Pharmacology S8

Question 1

Fibrinolytic Drugs mechanism of action

Answer 1

Amplify the conversion of an inactive enzyme precursor plasminogen to active enzyme plasmin.

Question 2

1 st generation thrombolytics

Answer 2

Streptokinase

Urokinase

Question 3

Clinical uses of thrombolytics

Answer 3

Myocardial infarction

• Pulmonary embolus ( massive )
• Acute ischaemic stroke

Question 4

Plasminogen

Plasmin

Answer 4

A single chain glycoprotein. 790 AA.

Converted to plasmin by cleavage of ARG560-Valine561 peptide band

Serine protease with trypsin like activity.

Attacks lysyl & arginyl bands of fibrin.

Question 5

Streptokinase

Answer 5

From -haemolytic streptococci

available as streptokinase ™

• Antigenic (bacterial origin) so only used once per patient *

Non enzymatic protein of beta-haemolytic streptococci.

Activates fibrinolytic system by forming 1:1 stoichiometric complex with plasminogen converting to active enzyme plasmin

Question 6

Urokinase

Answer 6

Trypsin –like serine protease of 2 polypeptide chains activates plasminogen directly converting it to plasmin.

Question 7

2 nd generation Thrombolytics

Answer 7

Anistrelplase

APSAC acetylation of plasminogen. T1/2 = 90mins. Permit bolus dosing. Less bradykinin produced than with Streptokinase ( hypotension )

Question 8

3 rd generation thrombolytics

Answer 8

Reteplase – recombinant plasminogen activator.

Half life 18mins 2 iv bolus injections 30mins apart Tenecteplase – multipoint mutation of parent

tPA

Question 9

3 rd generation thrombolytics

Give E

Answer 9

Reteplase

Tenecteplase

Question 10

phase-specific ca drugs

S-specific

M-specific

Answer 10

cytaribine

Vincristine

Question 11

Cell cycle specific drugs

Give examples

Answer 11

Antimetabolites 
Bleomycin peptide 
Antibiotics 
Vinca alkaloids 
Etoposide

Question 12

Cell cycle non specific drugs

Answer 12

Alkylation agents
Antibiotics
Cisplatin
Nitrosoureas

Question 13

Anthracyclines mechanism of action

Answer 13

Topoisomerase inhibition prevents the enzyme from religating cleaved DNA

Question 14

Anthracyclines

Give examples

Answer 14

doxorubicin

Question 15

Alkylating agents

mechanisms of action

Answer 15

formation of DNA cross links – interferes with cellular replication

Question 16

Alkylating agents

Give examples of

Answer 16

cyclophosphamide

Question 17

Antimetabolites

mechanisms of action

Answer 17

disrupt the synthesis of essential compounds required for cell synthesis

• • methotrexate inhibits the enzyme required to convert folate to its active form
• • cytarabine inhibits DNA synthesis

Question 18

Antimetabolites

Give examples

Answer 18

methotrexate inhibits the enzyme required to convert folate to its active form

• - cytarabine inhibits DNA synthesis

Question 19

Vinca Alkaloids

mechanisms of action

Answer 19

bind to tubulin – prevent formation of the mitotic spindle

Question 20

Vinca Alkaloids give examples

Answer 20

vincristine

Question 21

Reversal of heparin therapy with

Answer 21

Protamine sulphate

Question 22

Antidote of thrombolytics

Answer 22

tranexamic acid

Question 23

Major bleeds may need:

Answer 23

blood, fresh plasma plasma, cryoprecipitate, recombinant clotting factors