Pharmacology Flashcards
(115 cards)
1
Q
Is Acyclovir nephrotoxic?
A
Yes
(May cause crystalline nephropathy)
2
Q
Mechanism of Action for Acyclovir
A
Guanosine analog, phosphorylated by thymidine kinase which in turn inhibits the viral DNA polymerase
3
Q
Indications for Acyclovir
A
HSV
VZV
4
Q
Adverse effects of Acyclovir
A
Crystalline Neuropathy
5
Q
MoA for Ganciclovir
A
Guanosine analog, phosphorylated by thymidine kinase which in turn inhibits the viral DNA polymerase
6
Q
Indications for Ganciclovir
A
CMV
7
Q
Adverse Effects of Ganciclovir
A
Myelosuppression/agranulocytosis
8
Q
MoA of Ribavirin
A
Guanosine analog which inhibits inosine monophosphate (IMP) dehydrogenase, interferes with the capping of viral mRNA
9
Q
Indications for Ribavirin
A
Chronic hepatitis C, RSV
10
Q
SE of Ribavirin
A
Haemolytic anaemia
11
Q
MoA of Amantadine
A
Inhibits uncoating (M2 protein) of virus in cell. Also releases dopamine from nerve endings
12
Q
Indications for Amantadine
A
Influenza, Parkinson’s disease
13
Q
SE of Amantadine
A
Confusion, ataxia, slurred speech
14
Q
MoA of Oseltamivir
A
Inhibits neuraminidase
15
Q
Indications of Oseltamivir
A
Influenza
16
Q
MoA of Foscarnet
A
Pyrophosphate analog which inhibits viiral DNA polymerase
17
Q
Indications of Foscarnet
A
CMV, HSV if not responding to aciclovir
18
Q
SE of Foscarnet
A
Nephrotoxicity, hypocalcaemia, hypomagnasaemia, seizures
19
Q
MoA of Interferon-α
A
Human glycoproteins which inhibit synthesis of mRNA
20
Q
Indications of Interferon-α
A
Chronic hepatitis B & C, hairy cell leukaemia
21
Q
SE of Interferon-α
A
Flu-like symptoms, anorexia, myelosuppression
22
Q
MoA of Cidofovir
A
Acyclic nucleoside phosphonate, and is therefore independent of phosphorylation by viral enzymes (compare and contrast with aciclovir/ganciclovir)
23
Q
Indications of Cidofovir
A
CMV retinitis in HIV
24
Q
SE of Cidofovir
A
Nephrotoxicity
25
Anti-retroviral agents used in HIV
Nucleoside analogue reverse transcriptase inhibitors (NRTI)
examples: zidovudine (AZT), didanosine, lamivudine, stavudine, zalcitabine
Protease inhibitors (PI)
inhibits a protease needed to make the virus able to survive outside the cell
examples: indinavir, nelfinavir, ritonavir, saquinavir
Non-nucleoside reverse transcriptase inhibitors (NNRTI)
examples: nevirapine, efavirenz
26
MoA od Doxycycline
Doxycycline is a tetracycline antibiotic which inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit. It is bacteriostatic and used for gram positive and gram negative infections.
27
Tetracyclines - inhibits protein synthesis by acting on the____________________
30S subunit of ribosomes
28
MoA of Macrolide Abx
Macrolide antibiotics, like clarithromycin, inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit. Used for gram positive and gram negative infections.
29
MoA of Penicillin Abx
Penicillin antibiotics, like benzylpenicillin, inhibit bacterial cell wall formation. Used for gram positive infections.
30
MoA of folate antagonists
Folate antagonists, like trimethoprim, inhibit folate metabolism by binding to dihydrofolate reductase. Used for gram positive and gram negative infections.
31
MoA of Nitroimidazole Abx
Nitroimidazole antibiotics, like metronidazole, cause DNA strand breaks. Used for anaerobic infections.
32
Which Abx inhibit cell wall formation?
peptidoglycan cross-linking: penicillins, cephalosporins, carbopenems
peptidoglycan synthesis: glycopeptides (e.g. vancomycin)
33
Which Abx Inhibits protein synthesis (by acting on the ribosome)?
50S subunit: macrolides, chloramphenicol, clindamycin, linezolid, streptogrammins
30S subunit: aminoglycosides, tetracyclines
34
Which Abx inhibits DNA Synthesis?
quinolones (e.g. ciprofloxacin)
35
Which Abx damages DNA?
metronidazole
36
Which Abx Inhibits folic acid formation?
sulphonamides
trimethoprim
37
Which Abx inhibits RNA synthesis?
Rifampicin
38
_______ is a P450 enzyme inductor
Rifampicin
39
_____ are inhibitors of the P450 enzyme system.
SSRIs (like Fluoxetine)
40
Is Grapefruit juice and inhibitor or inducer of the P450 enzyme system?
Inhibitor - results in higher circulating levels of the drug.
41
Give 4 examples of drugs that inhibit the P450 enzyme system.
Grapefruit Juice
antibiotics: ciprofloxacin, erythromycin
isoniazid
cimetidine,omeprazole
amiodarone
allopurinol
imidazoles: ketoconazole, fluconazole
SSRIs: fluoxetine, sertraline
ritonavir
sodium valproate
acute alcohol intake
quinupristin
42
Inductors of the P450 enzyme system.
Induction usually requires prolonged exposure to the inducing drug, as opposed to P450 inhibitors, where effects are often seen rapidly
Inducers of the P450 system include
antiepileptics: phenytoin, carbamazepine
barbiturates: phenobarbitone
rifampicin
St John's Wort
chronic alcohol intake
griseofulvin
smoking (affects CYP1A2, reason why smokers require more aminophylline)
43
MoA of Tacrolimus
Tacrolimus is a calcineurin inhibitor used as an immunosuppressant to prevent transplant rejection. It has a very similar action to ciclosporin.
Mechanism of action
decreases clonal proliferation of T cells by reducing IL-2 release
binds to FKBP forming a complex which inhibits calcineurin, a phosphotase that activates various transcription factors in T cells
this contrasts with ciclosporin, which binds to cyclophilin rather than FKBP
44
SE of Tacrolimus
Tacrolimus is more potent than ciclosporin and hence the incidence of organ rejection is less. However, nephrotoxicity and impaired glucose tolerance is more common
45
Erythromycin can cause a ______ ___ _________
prolonged QT interval
46
Patients with lithium toxicity would present with ______________________________
diarrhoea, vomiting, lack of coordination, coarse tremors and agitation.
47
Abrupt withdrawal of beta-blockers can cause __________
'rebound tachycardia'
48
Indications for Beta Blockers
angina
post-myocardial infarction
heart failure: beta-blockers were previously avoided in heart failure but there is now strong evidence that certain beta-blockers improve both symptoms and mortality
arrhythmias: beta-blockers have now replaced digoxin as the rate-control drug of choice in atrial fibrillation
hypertension: the role of beta-blockers has diminished in recent years due to a lack of evidence in terms of reducing stroke and myocardial infarction.
thyrotoxicosis
migraine prophylaxis
anxiety
49
Examples of Beta Blockers
atenolol
propranolol: one of the first beta-blockers to be developed. Lipid soluble therefore crosses the blood-brain barrier
50
SE of Beta Blockers
bronchospasm
cold peripheries
fatigue
sleep disturbances, including nightmares
erectile dysfunction
51
CI for Beta Blockers
uncontrolled heart failure
asthma
sick sinus syndrome
concurrent verapamil use: may precipitate severe bradycardia
52
Thiazides may cause __________
hypokalaemia
53
NSAIDs reduce the anti-hypertensive effects of _____________
ACE inhibitors
54
ACE inhibitors
Angiotensin-converting enzyme (ACE) inhibitors are now the established first-line treatment in younger patients with hypertension and are also extensively used to treat heart failure. They are known to be less effective in treating hypertensive Afro-Caribbean patients. ACE inhibitors are also used to treat diabetic nephropathy and have a role in the secondary prevention of ischaemic heart disease.
55
MoA of ACE inhibitors
inhibits the conversion angiotensin I to angiotensin II
→ decrease in angiotensin II levels → to vasodilation and reduced blood pressure
→ decrease in angiotensin II levels → reduced stimulation for aldosterone release → decrease in sodium and water retention by the kidneys
renoprotective mechanism
angiotensin II constricts the efferent glomerular arterioles
ACE inhibitors therefore lead to dilation of the efferent arterioles → reduced glomerular capillary pressure → decreased mechanical stress on the delicate filtration barriers of the glomeruli
this is particularly important in diabetic nephropathy
ACE inhibitors are activated by phase 1 metabolism in the liver
56
SE of ACE inhibitors
cough
occurs in around 15% of patients and may occur up to a year after starting treatment
thought to be due to increased bradykinin levels
angioedema: may occur up to a year after starting treatment
hyperkalaemia
first-dose hypotension: more common in patients taking diuretics
57
CI of ACE inhibitors
pregnancy and breastfeeding - avoid
renovascular disease - may result in renal impairment
aortic stenosis - may result in hypotension
hereditary of idiopathic angioedema
specialist advice should be sought before starting ACE inhibitors in patients with a potassium >= 5.0 mmol/L
58
Interactions of ACE inhibitors
patients receiving high-dose diuretic therapy (more than 80 mg of furosemide a day)
significantly increases the risk of hypotension
59
Monitoring of ACE inhibitors
urea and electrolytes should be checked before treatment is initiated and after increasing the dose
a rise in the creatinine and potassium may be expected after starting ACE inhibitors
acceptable changes are an increase in serum creatinine, up to 30% from baseline and an increase in potassium up to 5.5 mmol/l.
significant renal impairment may occur in patients who have undiagnosed bilateral renal artery stenosis
60
Examples of ACE inhibitors
ramipril
enalapril
lisinopril
61
______________- inhibits sodium reabsorption by blocking the Na+-Clˆ’ symporter at the beginning of the distal convoluted tubule
Thiazides/thiazide-like drugs (e.g. indapamide)
62
SE of thiazide diuretics
dehydration
postural hypotension
hypokalaemia
due to increased delivery of sodium to the distal part of the distal convoluted tubule → increased sodium reabsorption in exchange for potassium and hydrogen ions
hyponatraemia
hypercalcaemia
the flip side of this is hypocalciuria, which may be useful in reducing the incidence of renal stones
gout
impaired glucose tolerance
impotence
Rare adverse effects
thrombocytopaenia
agranulocytosis
photosensitivity rash
pancreatitis
63
___________ is an example of a steroid with very high glucocorticoid activity, minimal mineralocorticoid activity
Dexamethasone
64
Minimal glucocorticoid activity, very high mineralocorticoid activity
Fludrocortisone
65
Glucocorticoid activity, high mineralocorticoid activity
Hydrocortisone
66
Predominant glucocorticoid activity, low mineralocorticoid activity
Prednisolone
67
Very high glucocorticoid activity, minimal mineralocorticoid activity
Dexamethasone
Betmethasone
68
Endocrine Glucocorticoid side-effects
impaired glucose regulation
increased appetite/weight gain
hirsutism
hyperlipidaemia
Cushing's syndrome
moon face
buffalo hump
striae
69
MSK Glucocorticoid side-effects
osteoporosis
proximal myopathy
avascular necrosis of the femoral head
70
Immunosuppressive Glucocorticoid side-effects
increased susceptibility to severe infection
reactivation of tuberculosis
71
Psychiatric Glucocorticoid side-effects
insomnia
mania
depression
psychosis
72
GI Glucocorticoid side-effects
peptic ulceration
acute pancreatitis
73
Ophthalmic Glucocorticoid side-effects
glaucoma
cataracts
74
suppression of growth in children
intracranial hypertension
neutrophilia
are all SE caused by ________
Glucocorticoids
75
Mineralocorticoid side-effects
fluid retention
hypertension
76
___________ reduce the peripheral breakdown of incretins such as GLP-1
Gliptins (DPP-4 inhibitors) e.g. alogliptin
77
Glucagon-like peptide-1 (GLP-1) mimetics (e.g. exenatide) MoA
These drugs increase insulin secretion and inhibit glucagon secretion.
78
Major advantage of using GLP-1 mimetics?
One of the major advances of GLP-1 mimetics is that they typically result in weight loss, in contrast to many medications such as insulin, sulfonylureas and thiazolidinediones. They are sometimes used in combination with insulin in T2DM to minimise weight gain.
79
Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. Vildagliptin, sitagliptin) MoA
dipeptidyl peptidase-4, DPP-4 inhibitors increase levels of incretins (GLP-1 and GIP) by decreasing their peripheral breakdown
80
__________ cause glycosuria
SGLT2 inhibitors
81
MoA for SGLT2 inhibitors
SGLT2 inhibitors block glucose reabsorption in the kidneys, leading to increased glycosuria (glucose excretion in urine) and a subsequent reduction in blood glucose levels
SGLT-2 inhibitors reversibly inhibit sodium-glucose co-transporter 2 (SGLT-2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion.
82
Advantage of SGLT2 inhibitors
offers more flexibility for the patient by reducing the risk of hypoglycemia, which can be an issue with certain diabetes medications, especially when the patient's meal schedule is unpredictable
Patients taking SGLT-2 drugs often lose weight, which can be beneficial in type 2 diabetes mellitus.
83
Examples of SGLT2 inhibitors
canagliflozin, dapagliflozin and empagliflozin.
84
SE of SGLT2 inhibitors
urinary and genital infection (secondary to glycosuria). Fournier's gangrene has also been reported
normoglycaemic ketoacidosis
increased risk of lower-limb amputation: feet should be closely monitored
85
MoA for Metformin
Metformin works by increasing insulin sensitivty and decreasing hepatic gluconeogenesis. It has no direct effect on insulin secretion from pancreatic beta cells, therefore, it cannot cause significant hypoglycaemia.
86
MoA for Insulin
Direct replacement for endogenous insulin
87
Main SE of Insulin
Hypoglycaemia
Weight gain
Lipodystrophy
88
MoA for Metformin
Increases insulin sensitivity
Decreases hepatic gluconeogenesis
89
Main SE of MEtformin
Gastrointestinal upset
Lactic acidosis
90
CI for Metformin
Cannot be used in patients with an eGFR of < 30 ml/min
91
MoA of Sulfonylureas (e.g. gliclazide and glimepiride)
Stimulate pancreatic beta cells to secrete insulin
92
SE of Sulfonylureas
Hypoglycaemia
Weight gain
Hyponatraemia
93
MoA of Thiazolidinediones (e.g. pioglitazone)
Activate PPAR-gamma receptor in adipocytes to promote adipogenesis and fatty acid uptake
94
SE of Thiazolidinediones (e.g. pioglitazone)
Weight gain
Fluid retention
95
DPP-4 inhibitors (-gliptins) MoA
Increases incretin levels which inhibit glucagon secretion
96
DPP-4 inhibitors (-gliptins) SE
Generally well tolerated but increased risk of pancreatitis
97
SGLT-2 inhibitors (-gliflozins) MoA
Inhibits reabsorption of glucose in the kidney
98
SGLT-2 inhibitors (-gliflozins) SE
Urinary tract infection
99
GLP-1 agonists (-tides) MoA
Incretin mimetic which inhibits glucagon secretion
100
SE of GLP-1 agonists (-tides)
Nausea and vomiting
Pancreatitis
101
True or false: Beta blockers inhibit the release of insulin.
True
102
What stimulates Insulin release?
Glucose
Amino acid
Vagal cholinergic
Secretin/Gastrin/CCK
Fatty acids
Beta adrenergic drugs
103
MoA of Carbimazole
Carbimazole blocks thyroid peroxidase from coupling and iodinating the tyrosine residues on thyroglobulin → reducing thyroid hormone production
in contrast propylthiouracil as well as this central mechanism of action also has a peripheral action by inhibiting 5'-deiodinase which reduces peripheral conversion of T4 to T3
104
SE of carbimazole
agranulocytosis
crosses the placenta, but may be used in low doses during pregnancy
105
MoA of Apremilast:
phosphodiesterase type-4 (PDE4) inhibitor
106
Indication of Apremilast
Apremilast is a phosphodiesterase type-4 (PDE4) inhibitor which can be used to treat active psoriatic arthritis (in combination with disease-modifying antirheumatic drugs or alone) in patients who have had an inadequate response or who have been intolerant to a prior disease-modifying antirheumatic drug therapy.
107
Give examples of anti-tumour necrosis factor (TNF) agents.
Adalimumab, etanercept and infliximab
108
Give an example of a dihydrofolate reductase inhibitor.
Methotrexate
109
Sulfasalazine is a prodrug for______which works through decreasing neutrophil chemotaxis alongside suppressing proliferation of lymphocytes and pro-inflammatory cytokines
5-ASA
110
Sulfasalazine is a disease modifying anti-rheumatic drug (DMARDs) used in the management of inflammatory arthritis, especially _____________. It is also used in the management of _______________
rheumatoid arthritis; inflammatory bowel disease.
111
Adverse effects of Sulfasalazine
oligospermia
Stevens-Johnson syndrome
pneumonitis / lung fibrosis
myelosuppression, Heinz body anaemia, megaloblastic anaemia
may colour tears → stained contact lenses
112
In contrast to other DMARDs, ________ is considered safe to use in both pregnancy and breastfeeding.
sulfasalazine
113
Methotrexate may cause _________ , so you should _______
hepatotoxicity - monitor LFTs
114
Ondansetron is a ______________antagonist
5-HT 3 serotonin
115
