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Y1B3 (CVS & IBL) 📘 > Pharmacology 💊 > Flashcards

Pharmacology 💊 Flashcards

1
Q

What is the source and chemistry of heparin?

A
  • Natural sulfated polysaccharide present in mast cells & carries –ve charge
  • It is high molecular weight 30000 dalton. “Widely changes which causes problems”
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2
Q

What is the route of administration of heparin?

A

Not taken orally as it precipitated by gastric HCl (given by IV, SC)

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3
Q

Does heparin cross BBB?

A

Cannot cross BBB or placenta (safe in pregnancy).

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4
Q

What is the onset and duration of heparin?

A

Rapid onset & short duration (t1/2 60 min.) “used in emergencies”

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5
Q

What is the mechanism of action of heparin?

A
  • Its action depends on the presence of a natural clotting inhibitor called antithrombin III.
  • Small quantities of heparin can activate antithrombin III inhibition of several clotting factors especially [factor X & thrombin (factor II)].
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6
Q

where does Heparin act?

A

In vivo & in vitro

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7
Q

What are the therapeutic uses of heparin?

A
  • Treatment of established thrombosis “prevent propagation”
  • Prevention of thrombosis “bid-ridden patients and artificial parts of the body”
  • Keep coagulation time & activated partial thromboplastin time (APTT) at 2-3 times of its normal value (for Control of Therapy).
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8
Q

What are the adverse effects of Heparin?

A
  • Bleeding is the most common and dangerous SE can be reversed by antidote protamine sulfate “physical antagonism” a basic +ve charged protein that combines with heparin.
  • Heparin-induced Thrombocytopenia “decreased platlets” (HIT) (autoimmune). arises from the development of antibodies to the heparin–platelet factor 4 complex. “Thrombocytopenia + thrombosis”
  • Hematoma if given IM
  • Osteoporosis
  • Alopecia
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9
Q

What is the nature of LMWH (enoxaparin)?

A

❖ Standard (unfractionated) heparin is a mixture of different molecular weight fractions (MW 3000-30,000 Da) that can affect more than one coagulation factor and produce thrombocytopenia (↑ risk of bleeding).

LMWH has molecular weight less than 8000 dalton which causes more specificity

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10
Q

What is the molecular weight of LMWH and what is the significance of that?

A

❖ LMWH has a MW less than 8000 Da that makes it specific for factor X with minimal effects on platelets and other clotting factors. “Not like heparin which activates antithrombin III that inhibits many factors”

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11
Q

Compare between unfractionated heparin and LMWH according to:-

Molecular weight range
anti-factor 10 activity
Nonspecific binding to plasma proteins
Bioavailability after subcutaneous injection
Half-life
Thrombocytopenia
Risk of bleeding
Lab monitoring
A

High - low

Less specific - more specific

High - low

Low (due to binding to S.C tissue) - High

Short (3 daily) - long (once daily)

Common 10% - less common (<2%) (less affinity for platlet factor 4)

High “all coagulation factors” - low

APTT (essential) - extent of inhibition of factor Xa (may br unnecessary)

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12
Q

Give examples for synthetic factor X inhibitors.

A

Fondaparinux

Rivaroxaban

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13
Q

What is the nature of Fondaparinux?

A

Synthetic pentasaccharide that have the same mechanism like LMWH (i.e. selective inhibitor of factor Xa).

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14
Q

What is the route of administration of Fondaparinux?

A

It is given by s.c. injection once daily (has long t1⁄2).

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15
Q

What is the route of administration and it is the mechanism of action of Rivaroxaban?

A
  • Oral inhibitor of (factor Xa).

- Bind to the active site of factor Xa Preventing its ability to convert prothrombin to thrombin

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16
Q

Give examples for direct thrombin inhibitors.

A

 Argatroban (parenteral)  Dabigatran (Oral)

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17
Q

What is the use of DTIs?

A

alternative to heparin to treat patients with heparin- induced thrombocytopenia

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18
Q

What is the Chemistry and nature of DTIs?

A

A “SDCTI” selective direct competitive thrombin inhibitor that binds to and inhibits both circulating and thrombus-bound thrombin (factor II a).

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19
Q

What is the source and the chemistry of warfarin?

A

Synthetic coumarin compound

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20
Q

What is bioavailability of warfarin?

A

Good (bioavailability is 100%).

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21
Q

Can warfarin pass BBB and the placenta?

A

Yes

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22
Q

Does warfarin bind highly to plasma proteins?

A

Highly bound to the plasma proteins “causes drug interactions”

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23
Q

What is the enzyme that is responsible for Biotransformation of warfarin?

A

hepatic CYP450.

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24
Q

What is the mechanism of action of warfarin?

A
  • Warfarin inhibits vitamin K epoxide reductase enzyme in the liver leading to inhibition of formation of the active form of vitamin K → ↓ synthesis of vitamin K-dependent clotting factors (II, VII, IX, and X).
  • The action of warfarin could be antagonized by vitamin K.
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25
Q

What are the therapeutic uses of warfarin?

A

Warfarin is given oral 2-10 mg/day for prevention and treatment of thrombosis. “But not in emergency”

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26
Q

How is warfarin monitored?

A
  • Monitoring is by prothrombin time (PT) or International Normalized Ratio (INR): It is the ratio of the PT in the patient to that of normal person.
  • It must be kept 2-3 times as the normal value. “Like heparin”
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27
Q

What are the adverse effects of warfarin?

A
  • Bleeding: gingival “related to gums” bleeding, nose bleeding…

 It could be treated by the following:
• Immediate stopping of the drug.
• Fresh frozen plasma (FFP). “Has clotting factors”
• Vitamin K1(phytomenadione): to enhance synthesis of clotting factors.

  • Teratogenicity: serious birth abnormalities “fetal warfarin syndrome”
  • Serious thrombosis: on sudden withdrawal
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28
Q

What are the drug interactions of warfarin?

A
  • Drugs that potentiate↑ warfarin action:
    1) Liquid paraffin: ↓ vit K absorption
    2) Oral antibiotics: ↓ vit K synthesis by killing the gut flora
    3) NSAIDs: displace warfarin from pp.
    4) Microsomal enzyme inhibitors (e.g. cimetidine, chloramphenicol) ↓ metabolism of warfarin.
  • Drugs that inhibit warfarin:
    1) Aluminum hydroxide: ↓ warfarin absorption
    2) Oral contraceptives and vit K. ↑ synthesis of clotting factors
    3) Microsomal enzyme inducers (e.g. phenobarbital, rifampin) ↑ metabolism of warfarin.
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29
Q

And compare between heparin and warfarin according to: –

Source
Action
Kinetics
Mechanism of action
Dose
Control
Onset
Duration
Antidote
A

Natural - Synthetic

In vivo and in vitro - In vivo

Absorbed from GIT, Cross the placenta and milk

It activates antithrombin III - They compete with Vit. K. on vit K epoxide reductase

S.C - oral

Blood coagulation time APTT - prothrombin time, INR

Immediate - Delayed1-3 days

Short 2-4 hrs - Long 4-7 days

Protamine sulphate + Fresh blood transfusion - Vitamin K +Fresh blood transfusion

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30
Q

why is pregnancy considered as a hypercoagulable state?

A

due to increase levels of coagulation factors and venous stasis.

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31
Q

What does pregnancy increase the risk of? “related to blood”

A

Pregnancy increases the risk of venous thrombosis and pulmonary embolism in susceptible female.

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32
Q

What does the use of warfarin in the first trimester and in the last trimester cause?

A

The use of warfarin in the first trimester is associated with birth defects (5%), while its use near full-term increases the risk of fetal hemorrhage.

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33
Q

What are the side effects of heparin and low molecular weight heparin during pregnancy?

A

Neither UFH nor LMWH cross the placenta; therefore, do not cause fetal bleeding or teratogenicity, but they can reduce bone mass density and cause osteoporosis if used through pregnancy.

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34
Q

What is anticoagulation recommended for pregnant women?

A

Anticoagulation is recommended in most pregnant patients with a mechanical heart valve.

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35
Q

What does the American College of chest physicals recommend regarding the use of anticoagulants during pregnancy?

A
  • The American College of Chest Physicians (ACCP) recommends the use LMWH until 13 weeks’ gestation, then change to warfarin until the patient is close to delivery (34 weeks), and then restart LMWH.
  • Long-term anticoagulants should be resumed postpartum
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36
Q

What are types of drugs used to stop coagulation? (Anti-platlets)

A

1- Aspirin (Acetyl salicylic acid)
2- ADP receptor blockers
3- Gp IIIA/IIB receptor blockers
4- PDE inhibitors

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37
Q

What is the mechanism of action of aspirin?

A
  • Irreversible inhibition of COX enzyme → ↓ TXA2 → ↓ platelet aggregation.
  • Irreversible acetylation of platelet cell membranes → ↓ platelet adhesions. “To collagen”
  • Decrease platelet ADP synthesis → decrease platelet accumulation
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38
Q

What is the duration of aspirin?

A

It lasts 7-9 days. “As it inhibits COX irreversibly, so new platelets must be formed”

“Platlets must be present in cases of surgery”

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39
Q

what are the types of doses of aspirin and what does each dose cause?

A
  • At higher doses (> 325 mg/day), aspirin may decrease endothelial synthesis of Prostacyclin (PGI2), which inhibits platelet activity
  • Low doses (75-150 mg/day) ↓ synthesis of platelet TXA2 “in platlets” more than PGI2 in endothelial cells and avoid this effect.
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40
Q

What are ADP receptor blockers?

A

Ticlopidine, Clopidogrel, Prasugrel

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41
Q

What is the mechanism of action of ADP receptor blockers?

A

Irreversibly inhibit the binding of ADP to its receptor “while aspirin prevents its synthesis” on platelets → inhibit the activation of the glycoprotein IIb/IIIa receptors “common on all antiplatlets” required for platelets to bind to fibrinogen and to each other

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42
Q

What is the nature of clopidogrel and what is the enzyme responsible for its biotransformation?

A

Is a prodrug → activated in the liver by CYP2C19.

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43
Q

What are poor metabolizers of clopidogrel?

A

Some people have genetic deficiency in the enzymes that metabolize clopidogrel; they are called “poor metabolizers” and cannot benefit from this drug.

“Those with liver problems as well”

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44
Q

What are the uses of clopidogrel?

A

❖ prophylaxis of thrombosis in both cerebrovascular and cardiovascular disease (e.g., coronary artery disease, coronary angioplasty, peripheral vascular disease, etc.).

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45
Q

What are gp IIb/IIIa receptor blockers?

A

Abciximab, Eptifibatide, Tirofiban

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46
Q

What is the nature of abciximab?

A

the Fab fragment of a monoclonal antibody

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47
Q

What is the nature of eptifdibatide?

A

small synthetic peptide “rattle snack venom”

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48
Q

What is the nature of tirofiban?

A

peptide of low MW

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49
Q

What is the mechanism of action of gp IIb/IIIa receptor blockers?

A

They bind to gp IIb/IIIa and blocks binding of platelets to fibrinogen. “Prevent final stage”

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50
Q

What are the uses of gp IIb/IIIa receptor blockers?

A

❖ Approved for use in patient undergoing percutaneous coronary intervention, for unstable angina, and for post-MI. “Revise the notes for these terms”

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51
Q

What is the mechanism of action of PDE inhibitors?

A

Dipyridamole inhibits phosphodiesterase (PDE) enzyme → ↑cGMP → VD and inhibition of platelet activity.

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52
Q

Give an example for PDE inhibitors.

A

Dipyridamole

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53
Q

What are the uses of PDE inhibitors?

A

limited to pro phylaxis (combined with warfarin ) in patients with prosthetic ( mechanical) heart valves.

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54
Q

What is the classification of fibrinolytics? “all IV”

A

Non-fibrin selective: Streptokinase and urokinase “bind to any plasminogen”

Fibrin selective: recombinant tissue plasminogen activator (rt-PA) “work on fibrin-bound plasminogen”

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55
Q

What is the nature of streptokinase and what is its mechanism of action?

A

Streptokinase is a protein that is isolated from streptococci; it activates plasminogen into plasmin non-enzymatically.

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56
Q

Is streptokinase antigenic?

A

It may be antigenic (causes allergy) in some people.

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57
Q

What is the nature of urokinase and what is it prepared from now?

A

Urokinase is a protease originally isolated from urine, It is now prepared in recombinant form from cultured kidney cells.

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58
Q

Which is more antigenic? streptokinase or urokinase

A

It is less antigenic than streptokinase.

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59
Q

Give examples for recombinant tissue plasminogen activators “the best fibrinolytics”

A

Alteplase, Reteplase, Tenecteplase

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60
Q

What differentiates recombinant tissue plasminogen activators?

A

They are most specific to fibrin-bound plasminogen

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61
Q

Are recombinant tissue plasminogen activators antigenic?

A

Not antigenic or allergic

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62
Q

What are the therapeutic uses of thrombolytic drugs?

A

❖ Acute myocardial infarction, ischemic stroke, pulmonary embolism, arterial thrombosis.

❖ In cases of acute MI, they should be given within 1h of onset. The maximum benefit is obtained if treatment is given within 90 minutes of the onset of pain. “The faster, the better”

❖ Before thrombolysis, care should be taken to ensure there is no liability for bleeding in a critical sit e.g., retina, CNS, etc.

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63
Q

What are the adverse effects of thrombolytic drugs?

A

1) Systemic bleeding is the major adverse effect:
- The risk is high with streptokinase and low with the recent recombinant tissue plasminogen activators.

2) Streptokinase can cause allergy, fever, and hypotension during I.V. infusion. (HAF)

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64
Q

What are types of coagulants and hemostatics?

A

Local agents and systemic agents

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65
Q

What are the local agents for coagulation and hemostatics?

A
  • Physical methods: application of pressure, cooling, or heat coagulation.
  • Vasoconstrictor drugs: e.g., adrenaline nasal pack in epistaxis.
  • Astringents: drugs which precipitate surface proteins e.g., Alum sulphate. “Close bleeding surface”
  • Thrombin and thromboplastin: applied on the bleeding surface as powders.
  • Fibrin and fibrinogen: available as dried sheets and used in surgery.
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66
Q

What are the systemic agents for coagulation and hemostatics?

A
  • Vitamin K: essential for synthesis of factors II, VII, IX, X by the liver.
  • Fresh blood or plasma transfusion: as sources of coagulation factors.
  • Plasma fractions:
    a) Thromboplastin (factor III): prepared from mammalian tissues.
    b) Antihemophilic globulin (factor VIII): given in hemophilia A.
    c) Calcium (factor IV): as a coagulation factor.
  • Aminocaproic acid and Tranexamic acid: inhibitors of fibrinolytic system.
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67
Q

What are the types of vitamin K?

A

1) Vitamin K1 (Phytomenadione):
- Naturally occurring fat-soluble vitamin present in green vegetables.
- It is available clinically in oral and parenteral forms.

2) Vitamin K2 is synthesized by intestinal bacteria.

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68
Q

What does vitamin K dissolve in?

A

Both vitamins K1 and K2 require bile salts for absorption “as they are fat soluble” “in case of oral” from the intestine.

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69
Q

What is the mechanism of action of vitamin K?

A

Vitamin K is required for posttranslational modification of clotting factors II, VII, IX, and X (1972) by liver cells.

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70
Q

What are the therapeutic uses of vitamin K?

A

1) To reverse bleeding episodes caused by overdose of warfarin, and salicylates.
2) To correct vitamin deficiency caused by dietary deficiency, or in patients receiving oral antibiotics. “That kill bacteria that form vit K”
3) To prevent hypothrombinemia of the newborn: all newborns should routinely receive 1–2 mg of vitamin K directly after birth (especially in premature infants).

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71
Q

What are the adverse effects of vitamin K?

A

Parenteral vitamin K1 is dissolved in oil; rapid i.v. administration can cause dyspnea, chest pain, or even death. “Must be slow”

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72
Q

What is the nature of caproic acid and tranexamic acid?

A
  • Aminocaproic acid is a synthetic agent that competitively inhibits plasminogen activation.
  • Tranexamic acid is more potent analogue of aminocaproic acid. “Gives same response with lower dose”
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73
Q

Give examples for fibrinolytic inhibitors

A

Aminocaproic acid and Tranexamic acid

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74
Q

What are the uses of fibrinolytic inhibitors?

A

1) To prevent bleeding from tissues rich in plasminogen activators e.g., lung, prostatic surgery, menorrhagia, and ocular trauma.
2) Prophylaxis for rebleeding from Intracranial aneurysm
3) As adjunctive therapy in hemophilia “added to something”
4) To stop bleeding caused by toxicity of fibrinolytic drugs

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75
Q

Why should hypertension be treated even if it was asymptomatic?

A

a) Damage to the vascular epithelium, paving the path for atherosclerosis, IHD, or nephropathy due to high intra-glomerular pressure
b) Increased load on heart due to high BP can cause CHF

‏ارتفاع الضغط حتى لو مش مسبب أعراض لكن ممكن يؤدي ‏لتصلب
الشرايين ومشاكل في الكلية

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76
Q

What are the types of hypertension?

A
  • According to the cause:
  • Essential hypertension. “Primary (90%)”
  • Secondary hypertension

According to the degree:

  • Normal blood pressure ≤120 ≤80
  • Stage 1 Hypertension 140–159 90–99
  • Stage 2 Hypertension 160–179 100–109
  • Stage 3 Hypertension ≥180 ≥110
  • Isolated systolic hypertension>140 <90
    “ISH respond more to CCBs”

“More than stage 3 —-> hypertensive emergency”

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77
Q

What is essential hypertension?

A
  • A disorder of unknown origin affecting the blood pressure regulating mechanisms
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78
Q

What is secondary hypertension?

A
  • Secondary to other disease processes
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79
Q

What is the target blood pressure for hypertensive patients?

A
  • For most patients, the goal of therapy is to maintain BP < 140/90 .
  • In patients with DM or chronic kidney disease, BP should be < 130/80
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80
Q

What does blood pressure equals?

A
  • Blood Pressure = (CO) X (PVR)
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81
Q

How is blood pressure physiologically maintained?

A
  • Physiologically BP is maintained by
    1) Arterioles
    2) post capillary venules
    3) Heart
    4) Kidney (volume of intravascular fluid)
  • Baroreflex and renin-angiotensin- aldosterone system regulates the above 4 sites
  • Local agents like Nitric oxide
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82
Q

What is abnormal about baroreflex and Renal blood volume control system in hypertensive patient?

A
  • Baroreflex and renal blood-volume control system set at higher level
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83
Q

How do all antihypertensive drugs work?

A
  • All antihypertensives act via interfering with normal mechanisms.
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84
Q

How is hypertension generally treated?

A

1) Non-drug therapy or life style modification

2) Anti-hypertensive drugs

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85
Q

What is non-drug therapy of hypertension?

A

1) Non-drug therapy or life style modification:
- Sodium restriction and potassium and Mg supplementation.
- Stop smoking and avoid stress.

  • Exercise and Weight reduction of obese patients.
    Control of risk factors: e.g. DM, hyperlipidemia, and obesity.
  • Avoid drugs that ↑ BP e.g.: sympathomimetics, sodium-containing drugs, oral contraceptives, corticosteroids.
  • Patients failing to normalize BP after 2 weeks of nonpharmacological therapy should be considered for drug treatment in addition to non drug therapy
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86
Q

What are antihypertensive drugs?

A

First choice groups (commonly used drugs):

  • ACEIs
  • Beta-blockers “2nd Line”
  • Calcium blockers
  • Diuretics

Second choice groups (used in special cases):

  • α1- blockers: prazosin.
  • Combined α and β-blockers: labetalol.
  • Adrenergic neuron blockers: α-methyldopa.
  • Vasodilators: hydralazine and diazoxide.
  • Central α2 stimulants: clonidine.
  • Dopamine agonists: fenoldopam.
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87
Q

Should RAAS be inhibited?

A
  • Inhibition of RAAS will correct hypertension but also will ↓ GFR and aggravate RF if renal ischemia was grave (S. creatinine is > 3 mg/dl).
  • So, if S. creatinine is up to 3 mg/dl (mild renal impairment) → you can safely block RAAS.
  • If creatinine>3 mg/dl (severe renal impairment) → blocking RAAS will aggravate RF.
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88
Q

what is the classification of ACE inhibitors?

A
  • SH-Containing drugs: Captopril

SH group may be responsible partially for immunological side effects “ATSL” e.g. angioedema, taste changes, skin rash and leukopenia.

  • Non SH-Containing drugs: ✓ Enalarpril ✓ fosinopril ✓ lisinopril ✓ benazepril ✓ ramipril

“FELRB”

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89
Q

What is the mechanism of action of ACE inhibitors?

A
  • They inhibit Ang-converting enzyme leading to Inhibition of Ang-II formation.
  • Also they Prevent degradation of bradykinin which is a potent VD.
  • ACEIs have direct arterio-veno dilator effects.
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90
Q

What are the pharmacological effects of ACE inhibitors?

A

1) They ↓ BP mainly by decreasing peripheral resistance
2) In presence of CHF, they ↑ COP due to reduction of both venous return (preload), and systemic BP (afterload).
3) They prevent cardiac remodeling “after MI”

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91
Q

What are the therapeutic uses of ACE inhibitors?

A

1) Systemic hypertension
2) Prevent LV remodeling after acute MI
3) Congestive heart failure (CHF)
4) Diabetic nephropathy & microalbuminuria

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92
Q

How do ACE inhibitors treat diabetic nephropathy and microalbuminuria?

A
  • They ↓ renal changes complicating diabetic nephropathy (mesangial cell apoptosis, proliferation, and collagen synthesis)
  • thus reducing microalbuminuria (provided that renal impairment is not grave).
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93
Q

What are the adverse effects of ACE inhibitors?

“No reflex tachycardia”

A

1) Dry Cough (the most common)
2) Angioedema (edema of the face and throat)
3) Aggravation of Proteinuria in patients with significant renal failure.
4) Taste changes
5) Orthostatic (First dose) hypotension
6) Teratogenesis (fetal pulmonary hypoplasia)
7) Skin rash.
8) Increased K+(hyperkalemia) due to ↓aldosterone release. “Should be used with K losing diuretics”

“AOT ATSL DryK”

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94
Q

What are the precautions that should be followed while using ACE inhibitors?

A
  • Start with small dose at bedtime.
  • Frequent monitoring of kidney functions (S. creatinine) and potassium levels one week after treatment and then every 3 months.
  • Avoid use of K+ sparing diuretics.
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95
Q

What are the contraindications of ACE inhibitors?

A

1) Hypotension: when systolic BP is less than 95 mm Hg.
2) Severe renal failure or bilateral renal artery stenosis (SCr> 3 mg/dl).
3) Pregnancy and lactation.
4) Hyperkalemia.

5) Neutropenia, thrombocytopenia, or severe anemia.
“Suppresses BM”

6) Immune problems.

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96
Q

What are examples of ARBs?

A

Losartan - Valsartan

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97
Q

What is the mechanism of action of ARBs?

A
  • They selectively block AT1 receptors.
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98
Q

How do ARBs have more efficacy than ACE inhibitors?

A
  • ACE inhibitors are Less effective because other enzymes rather than ACE can convert Ang-I into Ang-II
  • ARBs are More effective because it blocks AT-1 receptor, the final station responsible for Ang-II effects.
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99
Q

Is cough and angioedema common with ARBs?

A
  • Less frequent (they do not↑bradykinins)
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100
Q

Give an example for direct renin inhibitor.

A

Aliskiren

101
Q

What is a mechanism of action of Aliskirin?

A
  • It inhibits renin activity and consequently the RAAS.
102
Q

When is Aliskiren used?

A
  • Aliskiren is a recently approved drug for treatment of hyperreninemic hypertension.
103
Q

What is the rate limiting step in the formation of RAAS?

A
  • Activation of angiotensinogen into Ang-I by renin is the rate limiting step in formation of RAAS.
104
Q

What is the efficiency and side effects of Aliskirin comparable to?

A
  • The efficacy and side effects of aliskiren are comparable to ACEIs and ARBs.
105
Q

Revise the comparison between ACE inhibitors and ARBs

A

..

106
Q

What is the mechanism of action of calcium channel blockers?

A
  • block L type voltage-gated Ca2+ channels.

” Don’t affect skeletal muscles as they have calcium from inside unlike cardiac and smooth muscles which have there calcium from outside”

107
Q

What is the classification of calcium channel blockers?

A

According to tissue selectivity

  • CCB with mainly cardiac effects: verapamil, diltiazem.
  • CCB with mainly vascular effects (dihydropyridines): nifedipine, amlodipine
  • CCB with main effect on other tissue: flunarizine, cinnarizine.
108
Q

What is the mechanism of action of nifedipine and amlodipine?

“Amlodipine has higher duration and lower efficacy”

A
  • selective blockade of vascular Ca channels leads to vasodilatation which lower PVR and BP
109
Q

Which group of drugs has the highest smooth muscle relaxation and vasodilation action?

A
  • DHPs have highest smooth muscle relaxation and vasodilator action followed by verapamil and diltiazem
110
Q

What are the uses of Nifedipine /Amlodipine?

A
  • Hypertension
  • preterm labour
  • Peripheral vascular diseases

“HPP”

111
Q

What are the adverse effects of Nifedipine /Amlodipine?

A
  • Hypotension with reflex tachycardia with short acting version (not with nifedipine SR or amlodipine)
  • Gum hyperplasia
  • Ankle edema (due to salt and water retention by stimulated aldosterone release as physiological adaptation to hypotension
    ✓ Best managed by salt restriction, avoid prolonged standing and diuretics)

“HGA”

112
Q

What are the contraindications of Nifedipine /Amlodipine?

A

1) Hypotension

2) Hypertrophic obestructive cardiomyopathy (HOCM)
(as reflex tachycardia increase outflow obstruction)

3) Unstable angina (as reflex tachycardia increases the work of the heart and cardiac demands which may precipitate MI)
4) Supraventrecular tachycardia (SVT) (as reflex tachycardia may precipitate VT)

“HHAT”

113
Q

What is the mechanism of action of Verapamil, diltiazem?

A
  • Blockade of Ca channels in the vasculature, heart muscle and the AV node
114
Q

What are the main effects of Verapamil, diltiazem?

A
  • Negative ionotropic and chronotropic effects in heart
115
Q

What are the uses of Verapamil, diltiazem?

“Contraindications of nifedipine”

A

1) Ischemic heart diseases (as they decrease work of the heart ,produce coronary vasodilatation and decrease Ca causing apoptosis around the site of infarction)

2) Cardiac arrhythmias SVT
(as they cause AVN delay protecting the ventricles from the high rate of atria)

3) HOCM (as they decrease the force of ventricle contraction decreasing aortic outlet outflow obstruction)
4) Hypertension “last use as they are more effiecint on the heart”

116
Q

What are the adverse effects of Verapamil, diltiazem?

A
  • Bradycardia and heart block
  • Worsening of heart failure “unlike ACE inhibitors”
  • Constipation “Due to relaxation”
117
Q

What are the contraindications of Verapamil, diltiazem?

A
  • Bradycardia and heart block
  • Wolff-Parkinson-white syndrome (as they decrease AV nodal conduction, this stimulates passage of impulses through accessory conducting pathway between atria and ventricles causing atrioventricular re-entry tachycardia in WPWS)
118
Q

What are the drug interactions of Verapamil, diltiazem?

A
  • Caution for AV block with beta blockers, and digitalis (may precipitate heart block, nifedipine is best choice in such combination)
119
Q

What are the types of diuretics?

A

1) Thiazides: Hydrochlorothiazide, chlorthalidone
2) High ceiling: Furosemide
3) K+ sparing: Spironolactone, triamterene and amiloride

120
Q

What is the mechanism of action of diuretics?

A
  • Acts on Kidneys to increase excretion of Na and H2O → decrease in blood volume → decreased BP
121
Q

How is essential hypertension treated by diuretics?

A
  • Low dose of thiazide can be used as initial therapy in essential hypertension
  • Preferably should be used with a potassium sparing diuretic (for additive effect and correction of hypokalemia)
  • If therapy fails – another antihypertensive but do not increase the thiazide dose
122
Q

When are loop diuretics used for treatment of hypertension?

A
  • Loop diuretics are to be given when there is severe hypertension, complicated cases – CRF, CHF with retention of body fluids
123
Q

What are examples of beta blockers used in lowering blood pressure?

A
  • Propranolol is used in stage 1 and 2 HT alone or in combinations with a diuretic and/or vasodilator.
  • Labetalol can be given i.v. for hypertensive emergencies
124
Q

What is the mechanism of action of beta blockers and lowering blood pressure?

“CRAB VP”

A

1) Decrease (C)OP (-ve inotropic and chronotropic)
2) Decrease (r)enin release
3) Decreased (NE) release (blocks presynaptic 2 receptors)
4) Reconditioning of (b)aroreceptors.
5) Increase (p)rostaglandins.
6) Some blockers have (v)asodilator properties.

125
Q

What is the classification of vasodilators?

A

Arterio- dilators
Veno- dilators
Mixed dilators

126
Q

What are arterial dilators, their mechanism of action and uses?

A
  • Nifedipine – Hydralazine – Minoxidil– Diazoxide
  • They dilate arteries and ↓↓ BP (→↓ afterload)
  • They are used in severe systemic hypertension.
127
Q

What are veno-dilators, their mechanism of action and uses?

A
  • Nitrates
  • They dilate mainly veins→↓ venous return (→↓ preload) 
  • They are used in acute pulmonary edema.
128
Q

What are mixed dilators, their mechanism of action and uses?

A
  • Na nitroprusside– Prazosin – ACEIs
  • They ↓ preload & afterload
  • They are used in CHF.
129
Q

What are the general effects of vasodilators?

A
  • ↓ B. P → reflex sympathetic ++ → β1 ++→ HT → ↑ all cardiac properties→ ↑ HR (palpitation), ↑ COP blocked by Beta blockers.

Kidney

  • ↑ renin secretion.
  • cause salt & H2O retention.
130
Q

What is the mechanism of action of minoxidil?

A
  • direct arteriodilator by opening K+ channels→ hyperpolarization → relaxation of the vascular smooth ms.

“Prevent AP”

131
Q

What are the uses of minoxidil?

A
  • Chronic hypertension (oral) .
132
Q

What are the side effects of minoxidil?

A
  • stimulate hair growth (hypertrichosis), so it is used topically to prevent hair loss.
133
Q

What is the mechanism of hydralazine?

A
  • direct arterio-dilator.
134
Q

What are the uses of hydralazine?

A
  • severe hypertension and hypertension in pregnancy.
135
Q

What are the side effects of hydralazine?

A
  • SLE like syndrome in slow acetylators.
  • Mild arthritis,
  • Renal impairment
  • Skin rash.

“Auto-immune”

136
Q

What is the mechanism of diazoxide?

A
  • It is a direct arteriolo dilator by opening K+ channels→ hyperpolarization → relaxation of the vascular smooth ms.
137
Q

What are the uses of diazoxide?

A
  • It is given parenterally in hypertensive emergencies
138
Q

What is the mechanism of sodium nitroprusside?

A
  • It liberates nitric oxide (NO)→↑cGMP→ dilatation of both arteries and veins
139
Q

What are the uses of sodium nitroprusside?

A
  • It is given by i.v. infusion in hypertensive emergency and acute heart failure
140
Q

What are the side effects of sodium nitroprusside?

A
  • It can be converted to cyanide and thiocyanate.

- Accumulation of cyanide is minimized by sodium thiosulfate or hydroxocobalamin (vitamin B12).

141
Q

What is the structure of Diazoxide related to?

A
  • Structurally related to thiazides but it is not diuretic
142
Q

What is the mechanism of action of fenoldopam?

A
  • It stimulates peripheral dopamine (D1) receptors in renal and mesenteric arteries, leading to VD and decrease peripheral resistance.

“Inc work of kidney”

143
Q

What are the uses of fenoldopam?

A
  • It is used parenterally as a rapid-acting vasodilator to treat emergency hypertension in hospitalized patients.
144
Q

What are the drugs used in emergency hypertension?

A
  • Loop diuretics
  • Labetolol
  • Hydralazine
  • Diazoxide
  • Na Nitroprusside
  • Fenoldopam
145
Q

What is the drug used in essential HTN?

A
  • Patient <55 years old: ACEIs Patient
  • > 55 years old: CCBs “as they are more likely to have heart problems”
  • If not adequate, add thiazide or BB.
146
Q

What is the drug used in HTN + Pregnancy?

A

α-methyldopa, Labetalol, Nifedipine, Hydralazine

147
Q

What is the drug used in HTN + Diabetic nephropathy?

A

ACE inhibitors

148
Q

What is the drug used in HTN + DM?

A

ACEIs - ARBs

“Beta blockers are CI”

149
Q

What is the drug used in HTN + CKD?

A
  • S. creatinine<3 mg/dl: ACEIs

- S. creatinine>3 mg/dl: CCBs

150
Q

What is the drug used in HTN + CHF?

A

ACE inhibitors - diuretics

151
Q

What is the drug used in HTN + HF?

A

ACEIs - ARBs - Beta Blockers

152
Q

What is the drug used in HTN + BA?

A

CCBs

“Beta blocker and ACEIs are CI”

153
Q

What is the drug used in HTN + Angina?

A

CCBs - beta-blockers

154
Q

What is the drug used in HTN + thyrotoxicosis, sympathetic overactivity, or young patient with high plasma renin?

A

Beta-blockers

“To reduce the work of the heart”

155
Q

What is the drug used in HTN + BPH?

A

α1 blockers

156
Q

What is the drug used in pulmonary hypertension?

A

Endothelin receptor antagonists

157
Q

What is the drug used in post myocardial infarction hypertension?

A

Beta Blockers

158
Q

What is the drug used in dyslipidemias?

A

Alpha Blockers - CCBs - ACEIs - ARBs

159
Q

How is hypertensive emergency treated?

“In steps”

A
  • Hospitalization
  • Reduction of BP should be in hours and not in minutes
  • Drugs commonly used:
    1. Na nitroprusside, labetalol, fenoldopam, by slow i.v. infusion. “NLFF”
  1. Furosemide in volume overload (pulmonary edema & acute HF)
  2. Avoid Nifedipine, nitroglycerin, and hydralazine (rapid decrease of BP) “No NNH”
160
Q

What are ischemic heart diseases?

A
  • Chronic stable angina (Classic exertional angina) “effort”
  • Acute coronary syndromes (ACS): “rest and effort”
    A. Unstable angina
    B. Myocardial infarction “result from unstable angina”
  • Prinzmetal’s angina “rest and effort”
161
Q

What causes chronic stable angina (Classic exertional angina)?

A
  • It is due to atheromatous narrowing of the coronary artery.
162
Q

What are the symptoms of chronic stable angina?

A
  • Pain is induced by effort and disappears with rest.
163
Q

What causes unstable angina? And what causes myocardial infarction?

A
  • It is due to rupture of atheromatous plaque and formation of thrombus.
  • An intraluminal thrombus completely occludes the epicardial coronary artery at the site of plaque rupture leading to irreversible coagulative necrosis.
164
Q

What are the symptoms of unstable angina?

A
  • The patient experiences acceleration in the frequency or severity of chest pain, or new-onset angina pain.
165
Q

What are other names for Prinzmetal’s angina?

A
  • Variant angina; angina of rest; α-mediated angina
166
Q

What is the cause of Prinzmetal angina?

A
  • The coronary artery undergoes severe spasm due to overactivity of α1 receptors.
167
Q

What are the symptoms of Prinzmetal angina?

A
  • The patient develops pain at rest.
168
Q

How is stable angina managed?

A
  • Non-drug therapy = life style modification
  • Pharmacological therapy
  • Surgical treatment (myocardial revascularization)
169
Q

What is the non-drug therapy for stable angina?

A
  • Alteration of lifestyle
  • Correct obesity and reduce fat intake
  • Treatment of predisposing factors
170
Q

What is the pharmacological therapy for stable angina?

A
  • Immediate treatment of acute chest pain:
    ✓ Glyceryl trinitrate (GTN): sublingual or spray.
    ✓ Refer the patient to hospital if an ACS is suspected.
  • Long-term therapy:
    ✓ Beta-blockers: the first-line agents for chronic stable (exertional) angina.

✓ CCBs: the second-line agents for chronic stable angina

✓ Long and intermediate acting nitrates.

✓ Newer drugs: nicorandil , trimetazidine , Ivabradine, ranolazine

✓ Lipid lowering drugs: statins

✓ Antiplatelet drugs: e.g. aspirin, clopidogrel (see pharmacology of blood).

171
Q

What is the classification of organic nitrates and nitrites?

A

Glyceryl trinitrate (GTN)

Isosorbide dinitrate

Isosorbide mononitrate

172
Q

What is the onset of Glyceryl trinitrate (GTN), Isosorbide dinitrate and Isosorbide mononitrate Respictively?

A

Short - medium - long

173
Q

What is the route of adminstration of Glyceryl trinitrate (GTN), Isosorbide dinitrate and Isosorbide mononitrate Respictively?

A

SL/TD - SL/Oral - Oral

174
Q

What is the status of first pass metabolism of Glyceryl trinitrate (GTN), Isosorbide dinitrate and Isosorbide mononitrate Respictively?

A

Present - present - absent

175
Q

What is the onset of GTN?

A

1 – 5 min

176
Q

What is the duration of transdermal patches for treatment of angina?

A

10 hrs. duration

177
Q

When are GTN mainly used?

A
  • Relief of acute angina attack.
178
Q

When are isosorbide mononitrates mainly used?

A
  • Prophylaxis to prevent attacks
179
Q

What is the pharmacokinetics of organic nitrates and nitrites?

A
  • Absorption:
    ✓ Nitrates are rapidly absorbed from all sites of administration.
  • Metabolism: in the liver:
    ✓ If given oral → extensive first-pass metabolism (oral
    bioavailability <10%)
    ✓ If given sublingual → no first-pass metabolism → high
    bioavailability.
    ✓ Mononitrate: Has no hepatic metabolism → long duration of action.
  • Excretion:
    ✓ via the kidney.
180
Q

What is the mechanism of action of organic nitrates and nitrites?

A
  • Nitrates cause formation of the free radical nitric oxide (NO) which is identical to the endothelial derived relaxing factor (EDRF) → ↑ cGMP → VD (more on veins than arteries).
  • They also ↑ formation of vasodilator PGE2 and PGI2.
181
Q

What are the pharmacological effects of organic nitrates and nitrites?

“By two ways”

A

CVS: Blood vessels:
✓ VD of the venous (and to lesser extent the arterial) side leading to ↓ preload and ↓ afterload → ↓ cardiac work.
✓ VD of coronary arteries leading to increased coronary blood flow.
✓ VD of arteries in the face and neck leading to flushing of the face.
✓ VD of meningeal arteries leading to throbbing headache.

  • Heart: Reflex tachycardia (in high dose) 2ry to ↓ BP.
  • BP: High doses cause ↓↓ in both systolic and diastolic BP.
182
Q

What are the therapeutic uses of organic nitrates and nitrites?

A
  • Angina pectoris
  • Myocardial infarction: to ↓ the area of myocardial damage. “Just dec, no full treatment”
  • Acute heart failure: to ↓ preload and afterload.
183
Q

How do organic nitrates and nitrites treat angina pectoris?

A

✓ Nitrates are used for treatment of all types of angina both for relieving the acute attack and for prophylaxis.

✓ Decrease cardiac work & myocardial O2 demand through:
▪ Venodilatation → ↓ venous return (preload = ↓ end-diastolic pressure).
▪ Arteriolodilatation → ↓ peripheral resistance (afterload).

✓ Enhancement of coronary blood flow (perfusion) through:
▪ Coronary VD.
▪ Redistribution of blood from large epicordial vessels to
ischemic subendocardial vessels.

184
Q

What are the side effects of organic nitrates and nitrites?

A
  • Throbbing headache
  • Flushing of face
  • Orthostatic hypotension
  • Reflex tachycardia
  • Tolerance
185
Q

What causes tolerance to organic nitrates and nitrites?

A
  • Inactivation of mitochondrial enzyme
186
Q

How is tolerance to organic nitrates and nitrites managed?

A
  • Nitrate free period.
187
Q

What are the precautions that should be followed while nitrate therapy?

A
  • Check the expiry date (active tablets have burning taste).
  • Use the smallest effective dose to avoid hypotension and reflex tachycardia.
  • The patient should expel the SL tablet after pain relief.
  • The patient should consult his doctor if anginal pain does not improve after taking 3 SL tablets of NG during 15 min (the pain may be due to ACS)
  • Nitrates are contraindicated with sildenafil severe hypotension
188
Q

What are examples of beta blockers used in treatment of angina?

A
  • Nonselective (β1- & β2) ✓ e.g. propranolol
  • Cardioselective β1-blocker ✓ e.g. atenolol
  • β-blocker With α-blocking activity ✓ e.g., (β-blocker with VD effect) carvedilol
189
Q

What is a mechanism of action of beta blockers in treatment of angina?

A
  • Competitive inhibitors of catecholamine at β-adrenoceptors
  • Inhibit sympathetic stimulation of heart (β1) HR & contractility cardiac work & O2 requirement at rest and during exercise
190
Q

What is the clinical use of beta blockers in treatment of angina?

A
  • BB is the 1st choice in exertional angina
  • Absolutely CI in variant angina (because they block the β2- mediated coronary dilatation leaving the α1 receptors unopposed → ↑ coronary spasm).
191
Q

What are the side effects of beta blockers in treatment of angina?

A
  • Beta-1 effects:
    ✓ Bradycardia, heart block, heart failure
  • Beta-2 effects:
    ✓ bronchospasm, worsening PVD (peripheral vascular disease)
  • Others:
    ✓ Fatigue, depression, nightmares, impotence
192
Q

When are beta blockers contraindicated?

A
  • Variant angina (CI)
  • Asthma (CI)
  • Verapamil (CCB) and beta blockers are CI as both are myocardial depressants (inhibit conduction & contraction)
  • Avoid abrupt withdrawal
193
Q

What are examples of calcium channel blockers used in treatment of angina?

A
  • Verapamil
    ✓ Relatively cardioselective
    ✓ - ve chronotropic and inotropic
  • Nifedipine , amlodipine
    ✓ Smooth muscle selective
    ✓ Potent arterial dilator
  • Diltiazem
    ✓ Intermediate properties
194
Q

What is the mechanism of action of calcium channel blockers?

A
  • Block cardiac and smooth muscle voltage-gated L-type Ca++ channels
195
Q

What are the pharmacological effects of calcium channel blockers in treatment of angina?

A
  • Cardio-selective CCBs (verapamil & diltiazem):
    ✓ ↓↓ myocardial contractility and myocardial O2 demand.
    ✓ Produce coronary VD and ↑ coronary blood flow.
    ✓ ↓ Ca2+- mediated myocyte cell necrosis.
  • Nifedipine, amlodipine CCBs
    ✓ Vasodilator effect on resistance vessels → ↓↓ afterload
    ✓ Produce coronary VD and ↑ coronary blood flow.
196
Q

What is the Clinical use of calcium channel blockers in treatment of angina?

A
  • CCB is the 1st choice in variant angina

- Alternative to Betablockers (BB) instable angina if BB is contraindicated

197
Q

What are the advantages of combination of beta blockers with nitrates?

A
  • Combination of BBs and nitrates ↑ their efficiency & ↓ their side effects

“Check the table”

198
Q

Why shouldn’t nitrates be combined with nifedipine?

A
  • As it would cause severe hypotension and reflex tachycardia
199
Q

Why you shouldn’t beta blockers be combined with verapmil?

A
  • As it would cause heart block and Bradycardia
200
Q

What is additional therapy in treatment of stable angina?

A
  • Potassium-channel activators:(Nicorandil)

- Metabolic modulators (Cytoprotective)

201
Q

What is the mechanism of action of nicorandil?

A

✓ It combines activation, of the potassium k, channel with nitro- vasodilator (NO donor) actions.

✓ It is both an arterial and a venous dilator,

202
Q

What are the uses of nicorandil?

A

✓ It is used for patients who remain symptomatic despite optimal management with other drugs, often while they await surgery or angioplasty.

203
Q

What are the adverse effects of nicorandil?

A

✓ headache, flushing and dizziness.

“FHD”

204
Q

What are metabolic modulators (cytoprotective)?

A
  1. Na Channel blocker: Ranolazine
  2. Trimetazidine
  3. Ivabradine
205
Q

What is the mechanism of action of Na channel blocker (Ranolazine)?

“Dec intacellular Na which dec intracellular Ca”

A
  • It inhibits the late phase of the Na current →↓ intracellular Na →↓ intracellular Ca (↓ Ca overload that causes ischemia & death).
  • It has no effect on hemodynamic circulation.
206
Q

What are the uses of Ranolazine?

A
  • In chronic angina when other antianginal therapies fail
207
Q

What is the mechanism of action of trimetazidine?

“Enhances glocuse oxidation instead of fatty acids oxidation”

A
  • Inhibits beta-oxidation of fatty acids pathway in myocardium, which enhances glucose oxidation.
  • In an ischemic cell, energy obtained during glucose oxidation requires less oxygen consumption than in the beta-oxidation process.
208
Q

What is the use of trimetazidine?

A

Unstable angina, orally

209
Q

What is a mechanism of action of ivabradine? “Dec HR”

A
  • Selectively inhibits the pacemaker current leading to decrease cardiac pacemaker activity
  • Slowing the heart rate and allowing more time for blood to flow to the myocardium.
210
Q

What are other drugs used in management of angina?

A
  • Anti-platelets:
    Aspirin & clopidogrel
  • Other drugs
    1. Lipid-lowering therapy (statins): inhibit cholesterol synthesis in the liver
  1. ACE inhibitors: Reduction in preload and afterload, Reduction in left ventricular mass & inhibit pathological remodelling
211
Q

What is the most preferred and least preferred drugs in treatment of Angina with bronchial asthma?

A
  • Nitrates, CCBs

- Beta-Blockers

212
Q

What is the most preferred and least preferred drugs in treatment of Angina with heart failure?

A
  • Amlodipine

- Beta-Blockers

213
Q

What is the most preferred and least preferred drugs in treatment of Angina with hypertension?

A
  • Beta-Blockers, CCBs

- Nitrates

214
Q

What is the most preferred and least preferred drugs in treatment of Angina with DM?

A
  • Nitrates, Nifedipine

- Beta-Blockers, Verapamil

215
Q

How are acute coronary syndromes managed?

“‏مسكن + ‏أكسجين + ‏تذويب الجلطة + Nitrate or BB’

A

Hospitalization in CCU “MONA” + “T”

  • Morphine or Diamorphine
    ▪ Analgesia ▪ Afterload and Preload
  • Oxygen
  • Nitrates &/or Beta-blocker(Limit infraction size)
  • Aspirin &/or Clopidogrel
  • Anticoagulant &/or Thrombolytics
216
Q

What is the source of the digoxin?

A

– Natural plant derivatives (Foxglove plant).

217
Q

What is the chemistry of digoxin?

A

– Cardiac glycosides contain a lactone ring and a steroid (aglycone) moiety attached to sugar molecules.

218
Q

What is the pharmacokinetics of digoxin?

A

– Digoxin distributes to most body tissues and accumulates in cardiac tissue. The concentration of the drug in the heart is twice that in skeletal muscle and at least 15 times that in plasma.

– Has a long half-life 30 to 40 h.

– Elimination is renal. Dose adjustment should be done according to creatinine clearance.

219
Q

What is the mechanism of action of digoxin?

” Inc intracellular Na and Ca”

A
  • Digitalis ↑ cardiac contractility by increasing free intracellular Ca2+ through inhibition of membrane-bound Na+/K+ ATPase enzyme. This result in inhibition of Na+/K+ pump with
  • subsequent accumulation of intracellular Na+ and Ca2+ via:
    1. Increase Ca2+ release from the sarcoplasmic reticulum.
  1. Displacement of intracellular Ca2+ from its binding sites.
  2. Increased intracellular Na+ prevents Ca2+ expulsion from the cell by the Na+/Ca2+ exchanger.
220
Q

What are the autonomic effects of digoxin?

“Inc para and dec symp”

A

– ↑ vagal activity: By direct and indirect mechanisms (Central vagal stimulation, Reflex vagal stimulation: by sensitization of baroreceptors, ↑ sensitivity of SAN to A.Ch.

– ↓ sympathetic activity due to relieve of hypoxia & improved tissue oxygenation.

221
Q

What are the pharmacological effects of digoxin?

” + ino and bathmo tropic”
“- dromotropic”

A 
▪ ↑ Contractility and COP
▪ ↓ HR: (Bradycardia)
▪ Conduction velocity
▪ ↑ Excitability and automaticity
▪ ECG changes
▪ Normalization of arterial and venous pressures
222
Q

How does digoxin improve contractility and cardiac output?

A

due to +ve inotropic effect.

223
Q

What does improve in contractility due to digoxin lead to?

A
  • Improvement of RBF → diuresis and ↓ RAAS (i.e. ↓ fluid retention).
  • Relief of lung congestion.
224
Q

What causes Bradycardia on adminstration of digoxin?

A
  • ↑ vagal tone and ↓ sympathetic activity on the heart. - Direct inhibition of the AV conducting system
225
Q

What happens to conduction velocity due to administration of digoxin?

A
  • Intra atrial conduction: ↑ due to vagal stimulation.

- A-V conduction: ↓↓ by direct and vagal effects.

226
Q

What does increase in excitability and automaticity due to administration of digoxin lead to?

A

leading to ectopic foci and arrhythmia of any type (bigeminy, trigeminy, etc.).

227
Q

What are the ECG changes that happen upon administration of digoxin?

A
  • Prolonged PR interval.
  • Short QT interval.
  • ST segment depression & T-wave inversion.
228
Q

Why is arterial and venous pressure improved upon administration of digoxin?

A
  • due to improved hemodynamics.
229
Q

What is the drug of choice in case of chronic congestive heart failure associated with atrial flutter or fibrillation?

A

digoxin, because digoxin is the only drug that ↑ contractility and ↓ AV conduction in the same time.

230
Q

What is the drug of choice in cases of atrial flutter alone?

A

verapamil or beta-blockers are preferred.

231
Q

What is the drug of choice in cases of congestive heart failure not responding to other drugs?

A

Digoxin

232
Q

What is the initial degitalization of digoxin?

‏حباية في اليوم خمس مرات أسبوعيا

A

– It is done by giving one tablet 0.25 mg /day (5 days/week) from the start.

– The Cpss will be achieved after 5 t1⁄2 (t 1⁄2 = 40h i.e. after one week for digoxin).

– Rapid (loading) method is done in emergency conditions to achieve rapid Cpss. It is given as 2 tablets (0.5 mg) twice daily for 2 days(2x2x2).

233
Q

what is a maintenance dose of digoxin?

“Very narrow TI”

A

■ Maintenance dose: one tablet (0.25 mg)/day, 5 days/week.

234
Q

When is digoxin toxicity found?

A

When its plasma levels exceed 2 ng

235
Q

What are the precautions during digitalis therapy?

A

– Never give digitalis i.v. before being sure that the patient has not received digitalis during the last 14 days to avoid digitalis toxicity.

– Continuous monitoring of plasma K+ level.

– Mention all the relative contraindications.

236
Q

What are the absolute contraindication of digoxin?

A

– Heart block
– Hypertrophic obstructive cardiomyopathy (HOCM)
– Wolff-Parkinson-White (WPW) syndrome
– Paroxysmal ventricular tachycardia.

237
Q

What are the relative contraindications of digoxin?

A

– All causes of bradycardia.

– Systemic hypertension

– Pulmonary hypertension due to chronic lung disease:

– Cardiac diseases:
▪ Acute MI: digitalis ↑ the infarct size and aggravates arrhythmia.
▪ Cardiomyopathy…. digitalis is useless.

– Renal diseases: digoxin must be avoided in renal patients.

– In patients likely to require cardioversion: because digitalis may lead to fatal arrhythmia if given with cardioversion.

238
Q

What are the drugs that may interact with digoxin?

A

Antacids - Kaolin - Cholestyramine

Metoclopramide

Atropine

Quinidine

Loop diuretics and thiazides

239
Q

How do (Antacids - Kaolin - Cholestyramine) interact with digoxin?

A

Bind digoxin in the gut and decrease bioavailability (absorption)

240
Q

How do Metoclopramide interact with digoxin?

A

Increase gut motility leads to decrease digoxin absorption.

241
Q

How do Atropine interact with digoxin?

A

Decrease gut motility leads to increase digoxin absorption

242
Q

How do Quinidine interact with digoxin?

A

Decrease renal clearance of digoxin and displace digoxin from plasma proteins. Serum digoxin is increased.

243
Q

How do Loop diuretics and thiazides interact with digoxin?

A

Thiazides or loop diuretics may cause hypokalemia and hypomagnesemia which can ↑ the risk of digitalis toxicity

244
Q

What is the definition of heart failure?

A

Heart failure (HF) is a progressive clinical syndrome in which the heart is unable to pump sufficient blood to meet the metabolic demands of the body

245
Q

What is the pathophysiology of heart failure?

“Dec COP which activates RAAS and Sympathetic system, this is initially benefiting but eventually leads to deterioration of the cardiac function”

A

■ A reduction in COP lead to activation of the sympathetic nervous system and renin–angiotensin–aldosterone axis

■ Although initially beneficial, these alterations ultimately result in further deterioration of cardiac function.

246
Q

How is heart failure treated?

A

Non-drug therapy = life style modification

Drug therapy

247
Q

What is a non-drug therapy of heart failure?

A

– Rest.

– Dietary sodium (salt) and fat restriction.

– Avoid stress, smoking and alcohol.

– Weight reduction.

– Control of risk factors e.g. surgical correction of valvular diseases and treatment of hyperthyroidism, hypertension, etc.

– Avoid drugs that ↑ BP: e.g. sympathomimetics, sodium containing drugs, etc.

248
Q

What is the drug therapy or heart failure?

A

– Diuretics.

– ACEIs.

– Beta-blockers

– spironolactone.

– Vasodilators: nitrates and hydralazine

– Positive inotropic drugs:
▪ Cardiac glycosides (Digitalis).
▪ B1 agonist; dobutamine (used for short term only).
▪ Phosphodiesterase inhibitors: inamrinone & milrinone.

249
Q

What are the goals of therapy of heart failure?

“SS PR HS”

A
  • Relieve symptoms and signs (e.g. oedema)
  • Slow disease progression and cardiac remodeling
  • Reduce hospital admission
  • Improve survival

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