CPT to learn Flashcards
1
Q
general treatment for sickness
A
ondasteron (5HT3 inhibitor)
Cylizine (H2 receptor antagonist)
dexamethasone (corticosteroid)
2
Q
general treatment for sickness in pregnancy caused by hCG (hyperemesis gravidarum)
A
promethazine
metoclopramide
ondansetron
3
Q
A
4
Q
patients who use metformin need
A
good renal function
DDI
- ACEi (drugs which impair renal function)
- Diuretics (drugs which impair renal function)
- NSAIDs (drugs which impair renal function)
- Loop and thiazide like diuretics which increase glucose so can reduce metformin action
5
Q
types of B cell lymphoma
A
Diffuse large B-cell lymphoma (DLBCL)
Follicular lymphoma
6
Q
difference between X-rays in RA and OA
A
RA
- reduced joint space
- juxta artciular osteolytic lesions
- soft tissue damage
- deformity
OA
- osteophytes
- reduced joint space
- sclerotic lesions
- bony spurs
7
Q
how to diagnose lupus with acronymn
A
A RASH POINTS
8
Q
name the antiplatelet classes
A
Cyclo-oxygenase inhibitors
ADP receptor antagonists
Phosphodiesterase inhibitors
glycoprotein IIb/IIIa inhibitors
9
Q
active form of aspirin
A
hepatic hydrolysis to salicylic acid (active form)
10
Q
A
11
Q
MOA of ADP receptor antagonist prasrugel
A
- ADP receptor antagonist- inhibits binding of ADP to P2Y12 receptor
- Inhibiting activation of GPIIb/IIIa receptors (independent of COX pathway)
12
Q
CYP inhibitors
A
omeprazole (PPI)
ciprofloxacin (abx)
erythromycin (abx)
some SSRIs e.g. fluoxetine
grapefruit juie
amiodarone
disulfarim
13
Q
CYP inducers
A
phenytoin
carbamazepine
rifampicin
smoking
barbituates
sulphyureas
14
Q
Mode of action: Dipyridamole
A
- Inhibits cellular reuptake of adenosine–> increased plasma [adenosine] –> inhibits platelet aggregation via adenosine (A2) receptors
- Also acts as a phosphodiesterase inhibitor which prevents cAMP degradation –> inhibits expression of GP IIb/IIIa
- inhibits activation of platelets
15
Q
abcximab MOA
A
- Blocks binding of fibrinogen and von Willebrand factor (vWF)Abciximab= antibody- blocks GPIIb/IIIa receptors >80% reduction in aggregation – bleeding risk
- IV admin
- Target final common pathway- more complete platelet aggregation
16
Q
classes of lipid lowering drugs
A
statins
fibric acid derivatives (fibrates)
cholesterol absorption inhibitors
PCSK9 inhibitors
17
Q
Drug-drug interaction: Fenofibrate
A
warfarin- can increase the effects - bleeding
18
Q
Mode of action: Fenofibrate (fibric acid dervivative)
A
Activation of nuclear TF such as PPARα (peroxisome proliferation-activated receptor)
PPARα regulates expression of genes that control lipoprotein metabolism- increase production of lipoprotein lipase
- increase TAG from lipoprotein in plasma (lipolysis)
- increase fatty acid uptake by the liver
- increase HDL levels
- increase LDL affinity for receptor
19
Q
mode of action of cholesterol absoprtion inhibitors (Ezetimibe)
A
- inhibits NPC1L1 transporter at brush border
- reducing absorption of cholesterol by gut by 50%
- hepatic LDL receptor expression increase
- decrease in total cholesterol
20
Q
PCSK9 inhibitors mode of action
A
- LDLR on the liver cell surface binds to LDL and the LDLR–LDL complex is then internalized, after which the LDLR is normally recycled back to the cell surface
- PCSK9 binds to the LDLR on the surface of the hepatocyte, leading to the internalization and degradation of the LDLR in the lysosomes, and reducing the number of LDLRs on the cell surface.
- Inhibition of secreted PCSK9 by PCSK9 inhibitors therefore increases the number of available LDLRs on the cell surface and increase uptake of LDL‐C into the cell.
- lowering LDL in plasma
21
Q
main hypertension medication with example drug
A
ACEi (ramipril)
ARB (losartan and candesartan)
CCB
- dihydropyridine (nifedipine and amlodopine
-
non dihydropyridine
- phenylalkaline (veramapil)
- benzothiazepine (diltiazem)
Thiazide (bendroflumethiazide)and thiazide like diuretics (indapamide)
22
Q
which antihypertensives should never be prescribed together
A
B blocker and Non-dihydropyridine CCBs
(verapamil and diltiazem- asystole!!)
23
Q
name a drug under the drug class CA inhibitors
A
Acetazolamide
24
Q
Diuretic delivery to renal tubule and disease: liver disease
A
- Gut oedema- reduces absorption or oral diuretic
- Reduced albumin- furosemide needs to be bound to albumin to be delivered to the kidneys
- Bound to albumin so not filtered
- Actively transported into PCT lumen via Organic Anion Transporter with albumin
25
Bartter’s syndrome
* Genetic defects which cause cotransporter not to work
* **100% blockage of the Na+/K+/2Cl- channel**
* Like giving someone extreme furosemide
* Common symptoms include:
* muscle weakness, cramping and spasms
* fatigue
* excessive thirst (polydipsia)
* excessive urination (polyuria)
* nocturia
26
Gitelmans syndrome
* Genetic defects which cause cotransporter not to work
* **100% blockage of Sodium chloride channel**
* Like giving extreme thiazide
* Symptoms
* painful muscle spasms (tetany), muscle weakness or cramping,
* dizziness, and
* salt craving
27
Liddles sydrome
* **eNac channels** permanently turned on (dont need aldosterone) therefore excessive excretion of potassium and excessive reabsorption of sodium
* hypernatremia
* hypertension
* symptoms
* weakness
* fatigue
* palpitations
* muscular weakness
* shortness of breath
* constipation/abdominal distention
* exercise intolerance
* long-standing hypertension could become symptomatic.
28
DDI of loop diuretic
aminglycosides
- ototoxicity
- nephrotoxicity
29
NSAIDs and protein binding
NSAIDs displace other protein bound drugs- increasing free drug conc of other drugsParticularly high protein bound drugs
* MOA= competitive displacement
* Likely dose adjustment needed and increase monitoring
e.g.
* sulfonylureas- hypoglycaemia
* methotrexate – accumulation and hepatotoxicity
* warfarin- increased risk of bleeding
30
why does paracetamol have very little anti-inflammatory action
Related to peroxidases
Peroxide is important for the activity of paracetamol
In peripheral inflammation there is high levels of peroxidases which break down peroxide- therefore cant help with inflammation in peripheral tissue
31
renal considerations and NSAIDS
32
general MOA of corticosteroids
reduce transcription of IL-1 and IL-6
33
MOA of azathioprine
1. Azathiprine is cleaved to 6-MP
2. 6-MP is metabolised by TPMT to various molecules e.g. TIMP
3. TIMP further metapolises to 6-MeMPN (antimetabolite)
4. which inhibits purine synthesis
5. DNA and RNA need purines to be made
34
Mode of action Mycophenolate mofetil
Inhibits **inosine monophosphate dehydrogenase** (required for **guanosine** synthesis)
Impairs B and T cell proliferation
Spares other rapidly dividing cells (due to guanosine salvage pathways in other cells)
35
what to remember with methotrexate
GIVEN WEEKLY
## Footnote
Methotrexate competitively and reversibly inhibits dihydrofolate reductase (DHFR)
36
adverse drug response Anti-TNFa
TB reactivation is a risk
TNFa released by macrophages in response to M TB infection
TNFa is essential for development and maintenance of granulomata
Need to screen for latent TB before anti-TNF treatment
37
rituximab depletes
B cells by bidning to CD20 receptor on B cells
38
Q
How is acid produced by parietal cells
1. Carbonic anhydrase produces H2CO3 from water and carbon dioxide
2. This dissociates to form HCO3- and H+
3. H+ is pumped out of the cell on the apical membrane in exchange for potassium which comes into the cell
4. Potassium conc of the lumen is replenished by the K+ transporter
5. The chloride channel allows Cl- to move out of the cell into the lumen and combine with H+ à HCL
6. Meanwhile the Cl- conc of the cell is maintained by the HCO3-/Cl- antiport on the basal membrane
7. Influx of HCO3- into bloodstream= ALKALINE TIDE
39
confirmation of H.pylori infection
* Urea breath test
* Gastric urea= C12 isotopes (99%) and C13 isotopes= 1%
* Pts ingest urea with enriched C13
* H. pyrloi should convert this to ammonia and CO2
* Can detect C13 in exhaled CO2
* Stool antigen test
* Endoscopy with biopsy
40
H. pylori treatment
One week triple therapy
PPI + two antibacterial agents
* Lansoprazole + clarithromycin + amoxicillin OR
* Lansoprazole + clarithromycin + metronidazole (where allergic to amoxicillin )
Some evidence of local metronidazole resistance
Compliance with full course important for effectiveness and minimise risk of bacterial resistance
41
mesalazine first line treatment for
UC
## Footnote
Release of 5-aminosalsylic acid
Topical anti-inflammatory action at the colon (enteric coated tablets limit gastric breakdown)
**Mesalazine has no role in rheumatoid arthritis (no systemic effect)**
Sulfasalazine has more side effects so used infrequently for UC but sulfa group good for rheumatoid arthritis
42
Adverse drug response ICS
If taken correctly very few significant ADRS
Local immunosuppressive action e.g. candidiasis, horse voice (in pharynx)
Wash mouth out after
Pneumonia risk at high doses
43
Mode of action B agonists
* Bind to B2 receptors (GPCR)
* Increase cAMP
* Increase PKA
* Cause airway smooth muscle to relax
* Also increase mucus clearance by action of cilia
44
B agonist should alwyas be prescribed with
ICS
45
MOA of LTRA
Inhibit leukotrienes released by mast cells/eosinophils by blocking **CysLT1 receptor**
Reducing bronchoconstriction
Reducing mucus
Reducing oedema
46
define features of acute severe asthma
Unable to complete sentences
Peak flow 33-50% best or predicted
Respiratory rate ≥ 25/min
Heart rate ≥ 110/min
**Plus any of the following considered life-threatening:**
Peak flow \< 33% best or predicted (if recordable)
Arterial oxygen saturation (SpO2) \< 92%
Partial arterial pressure of oxygen (PaO2) \< 8 kPa
Normal partial arterial pressure of carbon dioxide (PaCO2) (4.6–6.0 kPa)
Silent chest, Cyanosis, Poor respiratory effort, Arrhythmia, Exhaustion, Altered conscious level, Hypotension
**treatment**
**Q**
**treatment of acute severe and life threatening asthma**
**A**
Oxygen!!
Increase to 94-98%
High dose (nebulised) B2 agonist- continuous if necessary
Driven in with oxygen
Oral steroid (prednisolone) should be prescribed for minimum 5 days (IV if not oral- preferably oral)
Continuous IC alongside
Nebulised ipratropium bromide (ipratropium) – short acting muscarinic antagonist (SAMA) alongside b2 agonist if poor response alone
Ipratropium less selective for M3 receptors compared to tiotropium, M2 activity too
Consider IV aminophylline if life threatening/near fatal and no success with above
Caution with taking PO theophylline
47
how do sodium channel blockers work in epilepsy
* Blocking of Na channels in central neurones
* This slows recovery of neurones from inactive to closed state
* Reduces neuronal transmission
48
Adverse drug response of Phenytoin
Exhibit **zero order kinetics**- care when adjusting doses
* Bone marrow suppression
* Hypotension
* Arrythmias (IV use)
49
levetiracetam
Option for focal seizures and generalised seizures
Anecdotally being used more frequently, easy dosing and well tolerated
**Safe in pregnancy**
**MOA**
* Novel mechanism of action
* **Synaptic vesicle glycoprotein binder.**
* Stops the release of neurotransmitters into synapse and reduces neuronal activity
50
inhibitors vs inducers
51
safest anti-epileptic for women of childbearing age
Lamotrigine and particularly Levetiracetam are the safest
52
what converts L-DOPA to dopamine
dopamine decarboxylase
53
parkinsons treatment
levodopa (LDOPA)
dopamine receptor agonists
MAOI type B inhibitors
COMT inhibitors
anticholinergics
54
LDOPA given with
peripheral DOPA decarboxylase inhibitor e.g. carbidopa or benserazide
--\> prevents conversion of L-DOPA to dopamine in the periphery= unpleasant side effects
55
dopamine is broken down by
COMT and MAOb
56
treatment with LDOPA requires
there to be enough substantia nigra cells left to convert LDOPA to dopamine
57
DDI LDOPA
Pyridoxine (vitamin B6) increases peripheral breakdown of L-DOPA
MAOIs risk hypertensive crisis
(not MOABIs at normal dose-lose specificity at high dose)
Many antipsychotic drugs block dopamine receptors and parkinsonism is a side effect (newer, ‘atypical’ antipsychotics less so)
58
name a dopamine receptor agonist
rotigone
59
name a MAOb inhibitor
selegiline
Inhibits monoamine oxidase B to decrease metabolism of dopamine and therefore increase amount found in synaptic cleft
prolong effect of LDOPA
60
COMT inhibitors
entacapone
No therapeutic effect alone (can use combination tablets COMT inhibitors and L-DOPA and peripheral dopa decarboxylase inhibitor- e.g. carbidopa
**Sinemet (carbidopa-levodopa) and Stalevo (carbidopa, levodopa, and entacapone)**
61
Drugs affecting neuromuscular transmission – exacerbate myasthenia gravis
Aminoglycosides
Beta-blockers, CCBs, quinidine, procainamide
ACE inhibitors
62
pharmacokinetics of Nitrofurantoin
Up to 50% of an oral dose Nitrofurantoin is excreted in the urine in unchanged form
This allows Nitrofurantoin to concentrate within urine, leading to more effective levels within the bladder than in other tissue compartments
This makes it one of the first-line agents in treating Urinary Tract Infections
63
quinolones e.g. cipro target
DNA gyrase (topoisomerase II)
64
side effects of quinolones
Tendinitis +/- rupture
Aortic dissection
Central nervous system effects (inc. Convulsions)
65
trimethoprim targets
folate synthesis ( inhibitor of dihydrofolate reductase,)
66
outline how opioid GPCR receptors decrease pai felt
* Agonist (opioid) binds to GPCR e.g. MOP receptor
* Leads to **decrease in cAMP**
* **Efflux of potassium**
* **Hyperpolarisation of membrane**
* Decreases substance P and GABA release
* Increases dopamine release
* Reveal Answer
67
Compared to morphine…fentanyl is
100x potency
Higher affinity for U (MOP) receptor
Less histamine release, sedation and constipation
68
Q
Contraindication buprenorphine
A
Hepatitis
Liver problems
Alcohol intoxication
Biliary and gall bladder problems
**Drug-drug interactions (many) buprenorphine**
- amiodarone
- amplodopine
69
Mode of action naloxone
Competitive antagonism of opioid – MU or MOP receptor
Blocks effect of other opioids e.g. morphine
Therefore increase in cAMP, increase pain, less of a high
Reveal Answer
70
opiod tolerance
1. **phosphorylation and ucnoupling** (think arrestin bidnin to U receptor due to chronic phosphorylation- GPCR unbinds)
* reduced decrease in cAMP
2. **cAMP production**
* when opioid stopped massive rebound of cAMP- withdrawal symptoms
71
factor Xa activates
prothrombin (II)--\> thrombin (IIa)
72
thrombin actiates
fibrinogen to fibrin ---\> fibrin clot
fibrin clot interacts with platelets
73
name some low molecular weight heparins (LMWH)
dalteparin, enoxaparin, fondaparinux
74
unfractionated heparin vs LMWH
both large negatively charged drugs which have poor GI absorption
- IV or Sc
75
Heparin induce thrombocytopenia (HIT)
Autoimmune response 2-14 days after initiation of heparin
* **Antibodies** to heparin **platelet factor 4 complex** produced
* Depletion of platelets
* but paradoxically can lead to thrombosis as more platelets activated by damaged endothelium
76
Heparin monitoring and reversal
* (activated) partial thomboplastin time (aPTT) when using therapeutic i.v. doses of UFH required – dose titrated/adjusted against this value
* LMWH much more predictable in its action so normally requires little monitoring
77
heparin reversal
**Protamine sulphate** forms inactive complex with heparin – given i.v. dissociates heparin from ATIII, irreversible binding amount given guided by heparin dose
Paradoxically can cause bleeding!?
Much greater effect with UFH than LMWH, no affect on fondaparinux
78
warfarin vs heparin
* Generally used in longer term anticoagulation compared to heparins
* Slow onset of action likely to require heparin cover (see later slides) if anticoagulation needed immediately
* **Good GI absorption and taken orally ~95+% bioavailability**
79
hepatic synthesis of which clotting factors requires vitamin K
clotting factors II, VII, IX and X (2,7, 9 and 10) requires vitamin K as cofactor for activation
warfarin is a vitamin K epoxide reductase inhibitor
80
can heparin or warfarin be used in pregnancy
heparin- yes
warfarin - no passes placenta
81
drug drug interaction warfarin
* Vitamin K intake e.g. fluctuating amount of green vegetable e.g. broccoli, cucumber
* Changes to gut bacteria e.g. cephalosporin antibiotic (reduces vitamin K)
* Alcohol
* Inhibition of CYP29C9 e.g. clopidogrel, alcohol, amiodarone
* Likely increase INR (more anticoagulated)
* Accelerated warfarin metabolism by inducers e.g. barbiturates, phenytoin, rifampicin, St Johns Wort
* Decrease INR- less anticoagulation
82
INR -international normalised ratio
* **Factor VII** most sensitive to vitamin K deficiency so used in prothrombin time - standardised against control plasma
* clotting time against a standard
* Allows for standard corrected value comparable across all laboratories
**aiming for an INR of 2.5**
DVT
PE
AF
83
aiming for an INR of 3.0 - 3.5
Recurrent DVT or PE in patients currently receiving anticoagulation
higher INR= more anticoagulated e..g takes 3.5x longer than average to clot
84
DOAC admin
oral
85
name three alkylating agent
* **Carmustine (BCNU)**
Alkylating compounds under the class **Platinum compounds:**
* **Cisplatin**
* **Oxaliplatin**
86
name 2 spinal poisons
A
Vinca alkaloids
Taxanes
87
name 2 antimetabolites
methotrexate
5-flourouracil
88
MOA of 5-fluorouracil
* 5-FU is converted to fluorodeoxyuridine monophosphate (FdUMP)
* FdUMP forms a stable complex with thymidylate synthase (TS), and thus inhibits deoxythymidine mono-phosphate (dTMP) production.
* **dTMP** is essential for DNA replication and repair and its depletion therefore causes cytotoxicity
89
methotrexate MOA
1. methotrexate competitively inhibits **dihydrofolate reductase (DHFR),** an enzyme that participates in the tetrahydrofolate synthesis.
2. The affinity of methotrexate for DHFR is about 1000-fold that of folate. DHFR catalyses the conversion of dihydrofolate to the active tetrahydrofolate.
3. Folic acid is needed for the de novo synthesis of the nucleoside thymidine, required for DNA synthesis.
4. Also, folate is essential for purine and pyrimidine base biosynthesis, so synthesis will be inhibited.
5. Methotrexate, therefore, inhibits the synthesis of DNA, RNA, thymidylates, and proteins
90
The fractional kill hypothesis states
that a defined chemotherapy concentration, applied for a defined time period, will kill a constant fraction of the cells in a population, independent of the absolute number of cells
91
chemotherapy adverse reactions
92
Q
Drug-drug interaction of COCP
* Oral contraceptive efficacy is reduced by enzyme (CYP450) inducing drugs- increasing the production of CYP450- therefore reduced plasma drug
* Antiepileptics such as carbamazepine or phenytoin
* Antibiotics e.g. rifampicin and rifabutin
* St Johns Wort
* Soya protein products enhance oestrogen absorption and reduce its storage in adipose and muscle so reduce half-life from 15 to 7 hours
93
menopause results in
high FSH
94
name a hormone replacement therapy
medroxyprogesterone acetate
95
adverse effects of POP
Spontaneous fetal abortion
Ectopic pregnancy
Headache
Breast tenderness
GI issues
96
bisphosphonates e.g. alendronic acid absopriton
must be taken on an empty stomach- absorption effected by contents of stomach
MOA
* Reduce bone turnover by reducing osteoclast activity
97
ADR of bisphosphonates
* Upper GI effects
* Oesophagitis (must stay seated or standing 30 mins after taking)
* Hypocalcaemia
* Check calcium and Vit D levels prior to initiating treatment
98
name a drug under the class of RU486
Mifepristone- abortion
**Progesterone and glucocorticoid receptor antagonist**
Therefore = anti-progesterone
* Sensitising the myometrium to prostaglandin- induced contractions
99
examples of drugs under the class SERM- selective oestrogen receptor modulator
Tamoxifen (breast cancer), Clomiphene (anovulation)
100
clomiphene MOA
Competes with oestrogen for ER binding
Leads to ovulation induction through increased production of anterior pituitary hormones (LH)
101
tamoxifen
Acts as a SERMconverse effects in breast and endometrial tissue
in endometrium = ER agonist
in breast = ER antagonist
cell cycle arrest
102
name a drug under the class Selective progesterone receptors modulators
Ulipristal acetate (e.g. ellaOne) - emergency contraception
103
define confounding factor
104
aim of placebo effect
Cancel out any placebo effect that may exist in the active treatment
105
Cytochrome P450 (CYPs)
Oxidation reaction most important
Found abundantly in smooth ER in hepatocytes
Numerous genes that encode these enzymes, CYP families 1-4 deals with most reaction
106
hydrophobic same as
lipophillic
107
to be eliminated drugs must be
hydrophillic
therefore hydrophobic drugs must be made more ionic by CYP450
108
age/hepatic disease and CYP
reduce activity of CYP- higher conc in blood
109
example of self induced metabolism of CYP
E.g. carbamazepine induces CYP3A4 and is also a substrate for CYP3A4
--\> reduce conc of carbamazepine
110
## Footnote
CYP 2D6
(substrates inc B-blockers, many SSRs and some opioids)
Missing in 7% of Caucasians
* Drug toxicity
* Cant metabolise drug
* Hyperactive in 30% east Africans
* Hard to get to therapeutic level of drugs
* E.g. wont feel effect of opioids
CYP 2D6 also inhibited by SSRIs, other antiarrhythmic agents and other antidepressants
111
ecretion of drugs
low weight- kidneys (OAT)
high molecular weight- liver - conjugated with glucoronic acid- excreted in faeces
112
loading dose equation
113
steady state
114
A new antiepileptic drug GSK7890 is undergoing phase II clinical trials. The average Vd has been reported as 70L and the overall clearance was 35 ml min-1 .
12) What is the t1/2 in hours for this new drug?
convert 35ml to 0.0351
0693 x 70/0.0351= 1,386
in hours
1,386/60= 23 hours
115
If clearance remains unchanged during the course of long term treatment and 10mg of drug is eliminated per day, what daily dose is required?
10mg of drug/day
clearance= administration
