Pharmacology Finals Flashcards
1
Q
What are the four basic stages of pharmacokinetics?
A
Absorption
Distribution
Metabolism
Elimination
2
Q
What protein in the blood would slow down the distribution process of a drug?
A
albumin
3
Q
Distribution of drug in the body depends on four main factors.
The first is blood flow, what are the others?
A
Lipophilicity (is the drug lipid soluble?)
Capillary permeability (Liver is more permeable than brain, so drug goes to Liver)
Plasma and Tissue Binding (albumin)
4
Q
What does the Volume of Distribution help predict?
A
Whether the drug will be concentrated in the blood plasma (eg. with albumin), or within the tissues.
5
Q
What do these have in common?
Phenytoin
Carbamazepine
Rifampin
Alcohol (Chronic)
Barbiturates
St. John’s Wort
PCRABS
A
Inducers of some of the main enzymes in Phase I cytochrome P450 reactions.
6
Q
What do these drugs have in common?
(CPACMAN)
Grapefruit
Protease inhibitors
Azole antifungles
Cimetidine
Macrolides (Except Azithromycin)
Amiodarone
Non-DHP CCBs (diltiazem and verapamil)
A
Inhibitors of some enzymes of cytochrome P450 pathway.
7
Q
What are the mechanisms of antibiotics? (6)
A
- inhibit cell wall synthesis
- inhibit cell membrane synthesis
- inhibit protein synthesis
- inhibit folate synthesis
- inhibit RNA polymerase
- inhibit DNA gyrase
8
Q
What four subgroup of antibiotics share the Beta-lactam structural ring?
(these antibiotics affect cell wall synthesis)
A
Penicillins
Cephalosporins (described by generations eg. 4th gen Cefepime)
Carbapenems
Monobactams
9
Q
What four things can antimicrobial drugs target?
A
- inhibiton of cell wall synthesis
- disruption of cell membrane function
- inhibition of nucleic acid synthesis
- inhibition of protein synthesis
- RNA synthesis
10
Q
How are penicillins and Cephalosporins eliminated?
A
via the kidneys
11
Q
Why aren’t cephalosporins routinally administered for chest infections?
A
Permit overgrowth of Clostrium difficile, and they alter normal flora in the gut (also the quinolones)
Also… insufficient activity against haemophilus influenzae
12
Q
What kind of drug is gentamicin?
A
aminoglycoside
13
Q
what is Gentamicin used for?
A
drug of choice for serious infections, eg. endocarditis, septicaemia, meningitis
14
Q
What are some adverse effects from Gentamicin?
A
- Nephrotoxicity
- Ototoxicity (8th cranial nerve - irreversible vestibular and auditory toxicity)
- neuromuscular paralysis
15
Q
What are the Five Rights?
A
Right Patient
Right Drug
Right Time
Right Dose
Right Route
16
Q
For women, what must you always ask?
A
Date of last menstrual bleed
17
Q
Why are bactericidal drugs more favourable than bacteriostatic?
A
- a faster microbiological response
- less likely to elicit microbial resistance
18
Q
Folate synthesis inhibitors (2)
A
- sulfanomides
- trimethoprim
19
Q
What are the narrow-spectrum penicillins?
A
Penicillin G
Penicillin V
flucloxacillin
20
Q
What are the extended-spectrum penicillins?
A
amoxicillin
ampicillin
piperacillin
ticarcillin
21
Q
what does MRSA stand for?
A
methicillin resistant Staphylococcus aureus
22
Q
Groups of antibiotics that are bacterial cell wall inhibitors (4)
A
- penicillins
- Cephalosporins
- monobactam
- others; vancomycin, fosfomycin
23
Q
what is Ceftazidime?
Kef- ta -zid -i -me
A
cephalosporin antibiotic, used in hospitals.
Cephalosporins
-antibacterials. interrupt cell wall biosynthesis
Used for pseudomonas aeruginosa
24
Q
Extended-spectrum penicillins are be subdivided into two groups, what are they?
A
- aminopenicillins (amoxcillin and ampicillin)
- antipseudomonal penicillins (piperacillin, ticarcillin)
25
What can amoxicillin treat **on its own?**
* upper respiratory tract infections
* community-acquired pneumonia
26
What is special about ***haemophilus influenzae*** and Moraxella catarrhalis?
These bacteria produce **pencillinase** , they need **clavulanate** combination.
27
What is vancomycin used for?
+ what happens if \>\> infusion rate?
MRSA (rem. **staphlococcus**) - given orally.
Adminstered parenterally to treat systemic infections.
\>\>\> infusion rate = hypotension, erythematous rash on face/ upper body "**red man syndrome"**
28
What can be used to treat (some strains of) **pseudomonas** **aeruginosa**?
antipseudomonal penicillins (eg. **piperacillin**)
29
why do bacterial protein synthesis inhibitors work?
due to differences in structure and function of **ribosomes** in prokaryotic and eukaryotic cells.
30
What three mechanisms do bacteria exert resistance to **Beta-lactam antibiotics?**
* inactivation of drug by **Beta-lactamase enyzmes** (main cause)
* reduced affinty of PBP for the antibiotics
* decreased entry od drugs into bacteria through outer membrane **porins**.
31
What is special about **gram -ve bacteria** and **penicillins**?
they are innately resistant to pencillins because if **impermeable** **porins** in outer membrane
32
What is doxycycline example of?
Doxycycline is a **broad-spectrum** antibiotic of the **tetracycline** class.
33
what is the most serious adverse effect of **aminoglycosides**? (2)
nephrotoxicity
ototoxicity
(most common cause of drug-induced renal failure)
rem. gentamicin, neomycin, stephomycin
34
name some groups of drugs that are bacteriostatic
**Sulfonamides** (block the synthesis of folic acid which is a cofactor for enzymes that synthesize DNA components and amino acids)
**tetracyclines** (because they **reversibly** inhibit bacterial protein synthesis)
35
way aren't **tetracyclines** very popular?
* because they are bacteriostatic.
* increased resistance.
* can cause **discolouration** of teeth if used by **pregnant women or children under eight years old.**
36
How do **tetracycline** antibiotics work?
**Inhibitor of bacterial protein synthesis**
(30s Ribosome subunit)
37
How do **macrolide** antibiotics work?
**Inhibit bacterial protein synthesis**
| (affect the 50s ribosomal subunit)
38
both **tetracyclines** and **macrolides** affect bacterial protein synthesis. Which is other main group that also affects **protein synthesis**?
**Aminoglycoside** (eg. streptomycin, gentamicin)
39
Inhibitors of bacterial protein synthesis..... (3)
**tetracyclines**
**macrolides**
**aminoglycosides**
40
Which **penicillins** are **anti**-**pseudomonal**?
piperacillin/ tazabactum
ticarcillin/ clavulanic acid
41
IMPORTANT
Which drug groups (according to modus operandi) are bacteriocidal?
Those that target :
**Cell Wall (van, pen, ceph)**
or
**Cell membrane (aminoglyc, polymyx)**
or
**DNA synthesis (metro, f/quin)**
42
Name the six classes of bacteriostatic antibiotics
* **Tetracyclines**
* Sulphonamides
* **Macrolides**
* Chloramphenicol
* **Trimethoprim**
* Spectinomycin
43
Name the six classes that are bacteriocidal
**All the b-lactam group**
(penicilliins, cephalosporins, monobactams, carbapenems)
**glycopeptides** (vancomycin)
**fluoroqinolones** (ciprofloxacin)
44
There are THREE narrow spectrum penicillins, what are they?
Penicillin G (Benzylpenicillin)
Pen V (Phenoxymethylpenicillin)
**Flucloxacillin**
**Unlike other penicillins,** flucloxacillin has activity against beta-lactamase-producing organisms such as Staphylococcus aureus
45
Name THREE broad spectrum penicillins
Amoxicillin/ co-amoxiclav
**ampicillin**
piperacillin with Tazobactam (Tazocin)
46
Which penicillin can great Staphylococcus aureus?
**flucloxacillin** has activity against beta-lactamase-producing organisms such as **Staphylococcus** **aureus** as it is **beta-lactamase stable**
47
What are common side effects of penicillins?
nausea, vomiting, diarrhoea
48
Which drugs target gram -ve?
Aminoglycosides
(eg. gentamicin)
Carbapenems
49
What drug would you use for serious infections? Endocarditis, septicaemia, meningitis?
Gentamicin
50
Gram +ve is the largest group of bacteria, give some examples.
Staphylococcus
Stephtococcus
Clostridium
Enterococus
Listeria
51
Give some examples of **gram -ve bacteria**
E. Coli
**Pseudomonas aeruginosa**
N. gonorrhoea
**chlamydia**
52
Vancomycin belongs to which group?
and how do they work?
Glycopeptides
Inhibit bacterial cell wall synthesis
53
There are two groups that are bacteriostatic and inhibitor folate synthesis. One group is sulfanomides, what's the other drug?
**Trimethoprim**
54
Quinolones/ floroquinolones. bacteriostatic or cidal?
Bacteriocidal... they are inhibitors of DNA gyrase.
55
What is flucloxacillin? And what makes it special?
Flucloxacillin is a **narrow-spectrum beta-lactam** antibiotic of the **penicillin** class.
It is used to treat infections caused by susceptible Gram-positive bacteria.
Unlike other penicillins, **flucloxacillin has activity against beta-lactamase-producing organisms such as Staphylococcus aureus** (not MRSA though)
56
What drug would treat chlamydia?
tetracycline
57
tetraycline cause teeth discolouration. What is another important adverse effect?
phototoxicity; need to be careful when sunbathing.
(safe after 18 weeks gestation)
58
Both these groups are inhibitors of bacterial protein synthesis, but they are different. **WHY**?
**aminoglycosides**
(eg. gentamycin)
**tetracyclines**
tetracyclines are bacteriostatic because reactions with bacteria are **reversible**.
59
Metronidazole
(nitroimidazole compound)
active against **anerobic protozoa.**
Also some anerobic bacteria; H.pylori, **C. difficle**
Drug of choice for amebiasis, giardiasis, trichomoniasis
60
What is the main use for **flucloxacillin**?
It's not inactivated by penicillinases, and thus effective in infections caused by **penicillin-resistant staphylococci.**
61
Piperacillin and Ticarcillin belong to which class of penicillins?
antipseudomonal
62
Name some macrolides
**Clarithromycin**
**Erthromycin**
**Azithromycin**
Telithromycin
63
How do macrolides work?
inhibit protein synthesis
64
Definition of pharmacodynamics
The study of the mechanism of action by which drugs produce their pharmacologic effects.
_The effect of the drugs on the body._
65
Definition of pharmacokinetics
How the body affects the drug
66
What is **efficacy of** a drug?
**The ability of a drug to initiate a cellular effect.** Also called instrinsic activity. NOT directly related to receptor affinity.
a full agonist has maximal efficacy, partial agonists will never have the same efficacy as full agonist.
67
What is potency?
a characteristic of drug action useful for **comparing different pharmacologic agents**.
68
What is **pharmacokinetics**?
the study of drug disposition in the body. **It focuses on the changes in drug plasma concentration**.
Plasma concentration will change according to absorption, distribution and elimination.
69
What is **pharmacodynamics**?
this is the study of the detailed **_mechanism of action_** by which drugs produce their pharmacologic effects.
70
**Trimethoprim**
moa, indications, side effects
**Antifolate** drug.
Weak base that concentrates in **acidic prostate tissues** and **vaginal fluid**s via **ion trapping**.
Often used for UTI.
SD: nausa, vomiting, epigastric distress, rashes, hepatitis, thrombocytopenia, leukopenia.
71
Ciprofloxacin
**Fluoroquinolone** group
Effective for many **gram -ve bacteria.**
Used to treat **anthrax** - postexposure prophylaxis of inhalational anthrax.
serious adverse effects; **tendonitis** and **tendon rupture**.
**alters** **blood glucose, phototoxicity, prolongation of QT interval**
Contraindicated; children, adolescents, pregnant and lactating women.
72
What is fluconazole?
Anti-fungal. Azole derivative
**excreted in the urine**, therefore can treat **vaginal candidiasis**
73
What is **metronidazole** used for?
Metronidazole is used to treat a wide variety of infections caused by **anaerobic bacteria** and **protozoa**.
Metronidazole is commonly prescribed to treat an infection called **bacterial vaginosis**. It is also prescribed before **gynaecological surgery** and surgery on the intestines to prevent infection from developing. It can safely be taken by people who are **allergic to penicillin.**
Metronidazole is also used to get rid of H**elicobacter pylori**.
Metronidazole is available as a **skin preparation** also.
First episode of **C. diff**
74
clarithromycin
macrolide
alternative to penicillin
indicated for chest infections, cellulitis, ear infections, H. pylori
75
what macrolide is indicated for acne?
erthromycin
(if tetracyclines not effective - doxycycline)
76
What are the characteristics of aminoglycosides, and give some examples.
**Gentamicin, Tobramycin** (very good for pseudomonas aeruginosa), s**treptomycin, neomycin** (very nephrotoxic).
**Bactericidal - interfer with protein synthesis.**
**Generally poorly absorbed from the gut**, and thus adminstered parenterally.
**They are not metabolised**, they are excreted primarily by the renal glomerular filtration.
Dosage must be **reduced in patients with renal impairment** because clearance is proportional to GFR (and creatinine excretion)
Active against wide range of aerobic **gram-negative** bacilli.
Most important side effects; **nephrotoxicity** and **ototoxicity**. Aminoglycosides are one of the most common causes of **drug-induced renal failure.** They can cause **acute tubular necrosis**.
Ototoxicity; can be both vesicular and cochlear toxicity. Often there is a delay between drug adminstration and onset of symptoms, px may have left the hospital.
77
What are the symptoms of vestibular toxicity that maybe associated with aminoglycosides?
dizziness, impaired vision, nystagmus, vertigo, nausea, vomiting, problems with postural balance and walking.
78
What are the symptoms of cochlear toxicity that maybe associated with aminoglycosides?
tinnitus, hearing impairment, irreversible deafness.
79
Some facts about cephalosporins
Third gen **Ceftazidime** (IV) is good for **pseudomonas** (HAP), 2nd gen cefuroxime can be used for CAP.
**B-lactam group**. 10% of px allergic to pencillin will be hypersenitive.
**Renally excreted**; dose reduction with renal impairment.
Can cause **pseudomembranous colitis** (swelling or inflammation of the large intestine) due to an overgrowth of Clostridium difficile.
80
Which antiobiotics are good for C. difficile?
**metronizaole**
and
**vancomycin** (could put in NG tube if px very unwell)
81
Key mechanism of Warfarin (coumarin compounds)
**Vitamin K antagonist**
Vitamin K is used to synthesis coagulation factors II (prothrombin), VII, IX, and X
82
Can Warfarin be used in pregnancy?
No because it crosses the placenta
83
Does Warfarin act immediately?
**No** because pool of circulating clotting factors needs to be depleted first.
Synthesis of **new** factors is then inhibited.
(takes 3-5 days to reach maximal effect)
84
What's the management of acute thromboembolic disorders?
LMWH (Low molecular weight heparin) plus warfarin, and then withdraw LMWH when warfarin is effective.
85
Patient advise for Warfarin
* Any signs of bleeding, including ecchymoses.
* Contraindicated in pregnancy (fetal warfarin syndrome)
* Avoid physical activities such as kick boxing
* Don't \>\>\> green vegetables (vit K)
* Avoid grapefruit juice, cranberry juice
* Avoid major weight changes
* Avoid aspirin, NSAIDs
86
Some common uses of Warfarin
Long-term treatment of **DVT**
Patients with **AF**
Patients with **artificial heart valves.**
87
Name three LMWHs
**enoxaparin**
dalteparin
tinzaparin
88
Key mechanism of heparin
**inactivates clotting factors** by **potentiating** the **activity** of an **endogenous anticoagulant** (antithrombin III)
89
Can Heparin be given orally?
No because heparin and related anticoagulants are not absorbed from the gut (large molecules) and so much be administered by IV.
90
What is antithrombin?
an endogenous anticoagulant (potent inhibitor of coagulation)
91
What is the principal component of fibrinolysis?
Enzyme plasmin
(generated from inactive precursor plasminogen)2
92
What are the key adverse effects of Heparin?
Bleeding
**thrombocytopenia**
(hyperkalemia)
93
What's the antidote for warfarin-induced bleeding
Phytonadione (vitamin K1)
94
Clinicial uses for Warfarin
Long term management of DVT, AF, and artificial heart values.
95
What is the INR for recurrent embolization or **artificial heart valves**?
What is the INR for warfarin (generally)
**3 - 4.5**
2-3
96
Name three **LMWH**
**enoxaparin**
**dalteparin**
**tinzaparin**
97
How does Dabigatran work?
**Direct thrombin inhibitor**
(thrombin is used in the pathway of transforming fibrinogen to fibrin)
98
How does LMWH compare to unfractionated heparin in it's modus operandi?
Primarily deactive factor X
99
What's the **advantages of LMWH** compared to standard heparin?
can be administered **subcutaneously**.
more **predictable** anticoagulation activity (aPTT monitoring not required)
100
What is HIT?
Heparin-induced-thrombocytopenia
101
Tell me about HIT 1
occurs in **25%** of patients. Direct interaction between heparin and platelets, leading to **platelet aggregation**. Mild and **reversible**.
102
Tell me about HIT 2
less common, **more serious**.
**Immunoglobulin** **mediated** platelet inactivation.
**High risk** of thrombotic complications and mortality.
103
How does **Fondaparinux** work?
**_Indirect_ Factor Xa inhibitor**
It s**electively binds to antithrombin** (an endogenous anticoagulant)
which
**inactivates Xa** resulting in a strong inhibition of thrombin generation and clot formation.
104
How Warfarin monitored?
**Prothrombin Time (PT)**
105
What does INR stand for?
International normalized ratio
INR = (PT observed / PT control)
PT = prothrombin time
106
What is the antidote to unfractionated heparin and LMWH?
**Protamine sulfate**
(+ve charged protein than combines with -ve charged heparin)
\*\* measure **aPTT** to monitor \*\*
107
How do you monitor
(a) Heparin
(b) Warfarin
(c) Dabigatran
(a) Heparin - aPTT
**(b) Warfarin - PT - Prothrombin Time (remember the INR equation for warfarin)**
(c) Dabigatran - TT (thrombin clotting time)
108
What initiates the formation of platelets along the vascular wall?
**injury** and the expose of the blood to extravascular **_collagen_**.
109
What activates the **intrinsic pathway**?
surface contact with a **foreign body** or **extravascular tissue** (i.e. collagen)
110
What activates the **extrinsic pathway** in the coagulation cascade?
a **complex tissue factor** called **thromboplastin**.
111
Where does the intrinsic and extrinsic pathways converge?
**Factor X -** major rate-limiting step
112
What does the activation of **factor X** lead to?
the formation of **Thrombin**
113
What three factors combined often lead to thrombic changes?
* **sluggish blood flow**
* inflammation
* **abnormalities in vascular endothelium**
114
What's the difference between arterial thrombi and venous thrombi?
**arterial thrombi** (white); more **platelet** aggrevation driven
**venous thrombi** (red); more **coagulation** driven
115
**Aspirin**; clinical usages and action as an antiplatelet drug
**Acute coronary syndrome**
**Thrombic strokes; acute and _prophylaxis_**
**shown to prevent MI with _angina_.**
Artificial heart valves, percutaneous coronary angioplasty.
ACTION: inhibits the synthesis of **prostaglandins** from **arachidonic acid.**
116
What's the most important **prostaglandin** affecting platelet aggregation?
**prostacyclin** and **TXA2**
(prostaglandin I2 (PGI2)
Aspirin irreversibly inhibits cyclooxygenase; enzyme that catalyzes TXA2 synthesis.
117
Adverse effects of **aspirin**
**GI bleeding**
**hypoprothrombinaemia**; therefore increased bleeding risks
118
When is clopidogrel indicated?
* px who can't tolerate aspirin
* used in **COMBINATION** with aspirin for **_ACS_**
119
When are the representative drugs **steptokinase, alteplase** indicated?
intravenously to degrade thrombi in px with
**MI, thromvotic stroke, PE**
Primary means of restoring coronary blood flow if angioplasty facilities not available.
120
Adverse reactions with aspirin?
GI irritation, bleeding,
hypersensitivity reactions,
tinnitus
121
Adverse reactions to **streptokinase**
bleeding, hypersensitivity reactions,
and reperfusion arrhymias (of interest)
**anaphylactic shock** can occur with streptokinase, therefore cannot be used repeatedly on same patient.
122
what is **t-PA** and give an example drug
**Alteplase**
drugs that are 'recombinant forms of human tissue plasminogen activator'
**tissue-Plasminogen Activator**
123
How do Rivaro**_xa_**ban, Api**_xa_**ban, Edo**_xa_**ban work?
Direct Factor **_Xa_** inhibitor
124
How does **_D_**agiba**_t_**ran work?
**_D_**irect **_t_**hrombin inhibitor.
125
What's best for arterial thrombosis? Anticoagulants or antiplatelets?
Antiplatelets
126
Some advantages of NOACs/ DOACs
* few interactions with food/ drugs
* predictable anticoagulant effect
* no need for routine monitoring
127
Which pathway does Warfarin affect?
Both intrinsic and extrinsic
128
MOA of **Heparin**
binds to body's **own anticoagulant (antithrombin III)**
This complex inhibits factor **Xa** (and other factors)
129
What is **Dipyridamole**?
What is it indicated for?
**Dipyridamole** a coronary vasodilator and a relatively weak antiplatelet drug.
**Dipyridamole** is used in **COMBO with aspirin** to prevent ischaemic stroke in px with history of thrombotic stroke, and persons experiencing TIAs.
130
What is Dipyridamole?
Dipyridamole is an **antiplatelet** medication that also has **vasodilating properties** that can make it **unsuitable** for use in those with severe coronary artery disease, unstable angina, recent myocardial infarction.
Can be combined with **aspirin** as an option to prevent occlusive vascular events in patients who have had a **TIA**, or **ischaemic stroke**.
131
What is prochlorperazine and what is it indicated for?
132
What is prochlorperazine?
What are it's indications?
**D2 receptor antagonist** ; this group acts primarily on the **CTZ** to inhibit stimulation of the **vomiting centre**.
Can also be given IV to treat **unremitting migraine** headache.
(rem that prochlorperazine is an anti-psychotic)
