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Clinical Pharmacology Flashcards

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1
Q

Acute intermittent porphyria

What drugs may precipitate attack?

AIP is caused by defect in porphobilinogen deaminase

A

Drugs which may precipitate attack in AIP
* barbiturates
* halothane
* benzodiazepines
* alcohol
* oral contraceptive pill
* sulphonamides

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2
Q

What is the effect of adrenaline?

Sympathomimetic amine - has both alpha + beta adernergic stim properties

A
  • Causes vasodilation
  • Increases vasoconstriction in skin + skidneys
  • Increases cardiac output and total peripheral resistance

Alpha adrenergic receptors
* Inhibits insulin secretion by pancreas
* Stimulates glycogenolysis in liver and muscle

Beta adrenergic receptors
* Stimulates glucagon secretion in pancrease
* Stimulates ACTH
* Stimulates lipolysis by adipose tissue

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3
Q

Give an example of beta1 and beta2 agonists

A

Beta-1 agonists
dobutamine

Beta-2 agonists
salbutamol

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4
Q

Give an example of alpha 1 and 2 agonists

A

Alpha-1 agonists
phenylephrine

Alpha-2 agonists
clonidine

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5
Q

Adrenoreceptor antagonists

Alpha-1 antagonist
Alpha-1a antagonist
Alpha-2 antagonist

A

Alpha antagonists
alpha-1: doxazosin
alpha-1a: tamsulosin - acts mainly on urogenital tract
alpha-2: yohimbine

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6
Q

Name a beta-1 antagonist and non-selective antagonist

A

Beta antagonists
beta-1: atenolol
non-selective: propranolol

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7
Q

Allopurinol interactions

A
  • Azathioprine
  • Cyclophosphamide - reduced renal clearance, marrow toxicity
  • Theophylline - increase plasma concentration
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8
Q

Describe the mechanism by which amiodarone causes hypothyroidism

A

The pathophysiology of amiodarone-induced hypothyroidism (AIH) is thought to be due to the high iodine content of amiodarone causing a Wolff-Chaikoff effect*
*an autoregulatory phenomenon where thyroxine formation is inhibited due to high levels of circulating iodide

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9
Q

Beta-blocker overdose
Features
Management

A

Features
* bradycardia
* hypotension
* heart failure
* syncope

Management
* if bradycardic then atropine
* in resistant cases glucagon may be used

Haemodialysis is not effective in beta-blocker overdose

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10
Q

Ciclosporin

A

nephrotoxicity
hepatotoxicity
fluid retention
hypertension
hyperkalaemia
hypertrichosis
gingival hyperplasia
tremor
impaired glucose tolerance
hyperlipidaemia
increased susceptibility to severe infection

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11
Q

Digoxin
MOA

A

Mechanism of action
* decreases conduction through the atrioventricular node which slows the ventricular rate in atrial fibrillation and flutter
* increases the force of cardiac muscle contraction due to inhibition of the Na+/K+ ATPase pump. Also stimulates vagus nerve
* digoxin has a narrow therapeutic index

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12
Q

Digoxin toxicity
Features

A

Features
* generally unwell, lethargy, nausea & vomiting, anorexia, confusion, yellow-green vision
* arrhythmias (e.g. AV block, bradycardia)
* gynaecomastia

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13
Q

Why is hypokalaemia a precipitating factor of digoxin toxicity

A

digoxin normally binds to the ATPase pump on the same site as potassium. Hypokalaemia → digoxin more easily bind to the ATPase pump → increased inhibitory effects

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14
Q

Management of digoxin toxicity

A

Management
Digibind
correct arrhythmias
monitor potassium

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15
Q

Drugs that cause impaired glucose tolerance

A

thiazides, furosemide (less common)
steroids
tacrolimus, ciclosporin
interferon-alpha
nicotinic acid
antipsychotics

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16
Q

Drug induced thrombocytopenia

A

quinine
abciximab
NSAIDs
diuretics: furosemide
antibiotics: penicillins, sulphonamides, rifampicin
anticonvulsants: carbamazepine, valproate
heparin

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17
Q

Drugs that cause urinary retention

A

tricyclic antidepressants e.g. amitriptyline
anticholinergics e.g. antipsychotics, antihistamines
opioids
NSAIDs
disopyramide

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18
Q

Side effects of sulfonylureas

A

Hypoglycaemic episodes
Increased appetite and weight gain
Syndrome of inappropriate ADH secretion
Liver dysfunction (cholestatic)

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19
Q

Side effects of glitazones

A

Weight gain
Fluid retention
Liver dysfunction
Fractures

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20
Q

Sife effects of isioniazid

A

mechanism of action: inhibits mycolic acid synthesis
peripheral neuropathy: prevent with pyridoxine (Vitamin B6)
hepatitis, agranulocytosis
liver enzyme inhibitor

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21
Q

Side effects of pyrazinamide

A

mechanism of action: converted by pyrazinamidase into pyrazinoic acid which in turn inhibits fatty acid synthase (FAS) I
hyperuricaemia causing gout
arthralgia, myalgia
hepatitis

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22
Q

Ethambutol
Side effect
MOA

A

mechanism of action: inhibits the enzyme arabinosyl transferase which polymerizes arabinose into arabinan
optic neuritis: check visual acuity before and during treatment
dose needs adjusting in patients with renal impairment

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23
Q

Cellular targets of drugs

Name 4 main types of cellular targets

A
  • Ligand gated Ion channels
  • G-protein coupled receptors
  • Tyrosine kinase receptors
  • Nuclear receptors
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24
Q

Ligand gated ion channel

A

Ion channel coupled to a membrane receptor causing direct signalling
Nicotinic acetylcholine receptor
GABA receptor

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25
# GPCR MOA Eg
* Drug binds to target that causes a sequence of events that leads to indirect signalling cAMP >> * Second messengers cause the effect * Adrenoreceptors
26
# Tyrosine kinase receptors MOA Eg
* When drug activates TKR, leads to phosphorylation that causes cell growth and differentiation * Insulin
27
# Nuclear receptors
* Receptors located on nucleus of cell and activation or inhibition of receptors via decreased/increased gene transcription * Lipid-soluble drugs can only work as they need to penetrate cell membrane to get to nucleus * After penetration, the drug can form complex with receptor protein * Levothyroxine, steroid, spironolactone, oestrogen
28
Drugs that cause photosensitivity
Causes of drug-induced photosensitivity thiazides tetracyclines, sulphonamides, ciprofloxacin amiodarone NSAIDs e.g. piroxicam psoralens sulphonylureas
29
# Antibiotics Name bactericidal antibiotic
penicillins cephalosporins aminoglycosides nitrofurantoin metronidazole quinolones rifampicin isoniazid
30
Bacteriostatic antibiotics Name 5
chloramphenicol macrolides tetracyclines sulphonamides trimethoprim
31
# HIV drugs What is the mOA of enfuvirtide and maraviroc
Entry inhibitors that prevent HIV-1 from entering and infecting immune cells
32
# HIV management Name some NRTIs
* Zidovudine * Abacavir * Emtricitabine * Didanosine * Lamivudine * Stavudine * Zalcitabine * Tenofovir
33
What is a general side effect of NRTI? Describe side effects Tenofovir Zidovudine Didanosine
* General side effects NRTI - peripheral neuropathy * Tenofovir - renal impairment osteoporosis * Zidovudine: anaemia, myopathy, black nails * Didanosine: pancreatitis
34
NNRTI Give 2 examples Give 3 general SE
Non-nucleoside reverse transcriptase inhibitors (NNRTI) examples: nevirapine, efavirenz side-effects: P450 enzyme interaction (nevirapine induces), rashes
35
What is the MOA of the following drugs Indinavir, nelfinavir, ritonavir, saquinavir Side effects
* Protease inhibitors * indinavir, nelfinavir, ritonavir, saquinavir * SE: diabetes, cushingoid
36
What is the MOA of raltegravir, elvitegravir, dolutegravir
Integrase inhibitors * block the action of integrase, a viral enzyme that inserts the viral genome into the DNA of the host cell * examples: raltegravir, elvitegravir, dolutegravir
37
# Drugs in managing LUTS Predominantly voiding symptoms - 'poor stream', what drugs are indicated?
* if 'moderate' or 'severe' symptoms offer an alpha-blocker * if the prostate is enlarged and the patient is 'considered at high risk of progression' then a 5-alpha reductase inhibitor should be offered
38
# Drugs in managing LUTS Predominantly overactive bladder
* antimuscarinic drugs should be offered if symptoms persist. NICE recommend oxybutynin (immediate release), tolterodine (immediate release), or darifenacin (once daily preparation) * Mirabregron
39
What do you give if a patient presented with mixed overactive and voiding symptoms
if there are mixed symptoms of voiding and storage not responding to an alpha blocker then a antimuscarinic (anticholinergic) drug may be added
40
What can be prescribed for nocturia
* advise about moderating fluid intake at night * furosemide 40mg in late afternoon may be considered * desmopressin may also be helpful
41
# Diabetic drugs Sulfonylureas MOA Common adverse effect
* They work by increasing pancreatic insulin secretion and hence are only effective if functional B-cells are present. * On a molecular level they bind to an ATP-dependent K+(KATP) channel on the cell membrane of pancreatic beta cells. * Hypoglycaemic episode * Weight gain | Tolbutamide, gliclazide
42
# Prescribing in renal failure Drugs to avoid in renal failure
* antibiotics: tetracycline, nitrofurantoin NSAIDs lithium metformin
43
# Prescribing in renal failure Which opioid is best?
Active metabolites of morphine accumulate in renal failure which means that long-term use is contraindicated in patients with moderate/severe renal failure. These toxic metabolites can accumulate causing toxicity and risk overdose. Oxycodone is mainly metabolised in the liver and thus safer to use in patients with moderate to end-stage renal failure with dose reductions.
44
# Antifungals Azoles
Mechanism of Action: Inhibits 14α-demethylase which produces ergosterol. Adverse Effects: P450 inhibition, Liver toxicity.
45
# Antifungals Amphotericin B
Mechanism of Action: Binds with ergosterol forming a transmembrane channel that leads to monovalent ion leakage (K+, Na+, H+, and Cl). Adverse Effects: Nephrotoxicity, flu-like symptoms, hypokalemia, hypomagnesemia. Notes: Used for systemic fungal infections.
46
# Antifungals Terbinafine
Mechanism of Action: Inhibits squalene epoxidase. Adverse Effects: Commonly used in oral form to treat fungal nail infections.
47
# Antifungals Griseofulvin
Mechanism of Action: Interacts with microtubules to disrupt the mitotic spindle. Adverse Effects: Induces P450 system, teratogenic.
48
# Antifungals Flucytosine
Mechanism of Action: Converted by cytosine deaminase to 5-fluorouracil, which inhibits thymidylate synthase and disrupts fungal protein synthesis. Adverse Effects: Vomiting.
49
# Antifungals Caspofungin
Mechanism of Action: Inhibits synthesis of beta-glucan, a major fungal cell wall component. Adverse Effects: Flushing.
50
# Antifungals Nystatin
Mechanism of Action: Binds with ergosterol forming a transmembrane channel that leads to monovalent ion leakage (K+, Na+, H+, and Cl). Adverse Effects: As very toxic, can only be used topically (e.g., for oral thrush).
51
# Diabetic drugs Gliptins - DPP4 inhibitors
* reduce the peripheral breakdown of incretins such as GLP-1 (incretins inhibit glucagon secretion and increase insulin secretion) * Dont confuse these with GLP-1 mimetics * Sitagliptin
52
# P450 enzyme system Inducers of P450 system will lead to lower drug levels (increased metabolism of drug)
antiepileptics: phenytoin, carbamazepine barbiturates: phenobarbitone rifampicin St John's Wort chronic alcohol intake griseofulvin smoking (affects CYP1A2, reason why smokers require more aminophylline)
53
# P450 system Inhibitors of the P450 system include
antibiotics: ciprofloxacin, erythromycin isoniazid cimetidine,omeprazole amiodarone allopurinol imidazoles: ketoconazole, fluconazole SSRIs: fluoxetine, sertraline ritonavir sodium valproate acute alcohol intake quinupristin
54
Phenytoin monitoring *Phenytoin is a medication that has a narrow therapeutic index, meaning there is a small difference between therapeutic and toxic levels. *
* Immediately before next dose (trough levels)
55
Side effect of finasteride
Works by metaboliseing testosterone Adverse effects impotence decrease libido ejaculation disorders gynaecomastia and breast tenderness
56
drugs causing urticaria
aspirin penicillins NSAIDs opiates
57
Octreotide MOA Indications SE
Overview long-acting analogue of somatostatin somatostatin is released from D cells of pancreas and inhibits the release of growth hormone, glucagon and insulin Uses acute treatment of variceal haemorrhage acromegaly carcinoid syndrome prevent complications following pancreatic surgery VIPomas refractory diarrhoea Adverse effects gallstones (secondary to biliary stasis)
58
# Antiarrhythmics: Vaughan Williams classification Quinidine Procainamide Disopyramide
Class 1a Block sodium channels Increases AP duration
58
# Anti-diabetic drug MOA of meglitinides
increase pancreatic insulin secretion like sulfonylureas they bind to an ATP-dependent K+(KATP) channel on the cell membrane of pancreatic beta cells often used for patients with an erratic lifestyle adverse effects include weight gain and hypoglycaemia (less so than sulfonylureas) repaglinide nateglinide
59
# Antiarrhythmics: Vaughan Williams classification Lidocaine Mexiletine Tocainide
Class 1b Block sodium channels Decreases AP duration
60
# Antiarrhythmics: Vaughan Williams classification Flecainide Encainide Propafenone
Class 1c Block sodium channels No effect on AP duration
61
# Antiarrhythmics: Vaughan Williams classification Propranolol Atenolol Bisoprolol Metoprolol
Class II Beta-adrenoceptor antagonists
62
# Antiarrhythmics: Vaughan Williams classification Amiodarone Sotalol Ibutilide Bretylium
Class III Blocks K+ channels
63
# Antiarrhythmics: Vaughan Williams classification Class IV
Verapamil Diltiazem CCB
64
Management of bulimia
High dose fluoxetine
65
Management of neuropathic pain if single agent not working
Drugs for neuropathic pain are typically used as monotherapy, i.e. if not working then drugs should be switched, not added
66
Procyclidine MOA
Antimuscarinic Used in PD treatment It blocks muscarinic acetylcholine receptors in the central and peripheral nervous system. This results in a reduction of cholinergic activity which helps to balance the dopamine-acetylcholine ratio in the brain
67
Mirabegron
beta 3 agonist
68
69
Management of metformin during Ramadhan
During Ramadan, one-third of the normal metformin dose should be taken before sunrise and two-thirds should be taken after sunset
70
Quinine what is a side effect related to the ear?
ototoxicity - tinnitus
71
Brupropion for smoking cessation - what is the MOA
The correct answer is Norepinephrine and dopamine reuptake inhibitor, and nicotinic antagonist. Bupropion is an atypical antidepressant and smoking cessation aid. Its primary mechanism of action involves the inhibition of the reuptake of norepinephrine and dopamine, thereby increasing their synaptic concentrations. It also acts as a non-competitive antagonist of nicotinic acetylcholine receptors, which is thought to contribute to its efficacy in smoking cessation.
72
# Mineral bone disease management in CKD 1-alpha hydroxylation normally occurs in the kidneys → CKD leads to low vitamin D the kidneys normally excrete phosphate → CKD leads to high phosphate How does this cause osteomalacia? How does this cause secondary hyperparathyroidism?
the high phosphate level 'drags' calcium from the bones, resulting in osteomalacia low calcium: due to lack of vitamin D, high phosphate secondary hyperparathyroidism: due to low calcium, high phosphate and low vitamin D
73
# Mineral bone disease management in CKD Management - aim to reduce phosphate, PTH levels
* Reduce dietary intake of phosphate * Use phosphate binders * Use alfacalcidiol, calcitriol * Parathyroidectomy
74
Why cant we just give calcium supplements to CKD patients?
* Alfacidiol is used instead in ESRD * Does not require activation in kidneys
75
What antibiotic is associated with skin pigmentation
Minocycline
76
Drugs causing haemolysis in G6PD
anti-malarials: primaquine ciprofloxacin sulph- group drugs: sulphonamides, sulphasalazine, sulfonylureas
77
Fluconazole and ciclosporin - what is the interaction
Fluconazole inhibits the metabolism of ciclosporin which increases the risk of ciclosporin nephrotoxicity.
78
MOA of oseltamivir vs aciclovir
Oseltamivir - Neuraminidase inhibitor Aciclovir - DNA polymerase inhibitor
79
Aspirin is reversible or non reversible cox inhibitor?
Reversible cox inhibitor causes anti-platelet effect by its impact on TXA2
80
What is the time lag of finasteride from initiation to when its effects are seen?
Up to 6 months. Finasteride, a 5-alpha reductase inhibitor, is used in the treatment of benign prostatic hyperplasia (BPH) and its effectiveness can take up to six months. This is because finasteride works by inhibiting the conversion of testosterone into dihydrotestosterone (DHT), which contributes to prostate enlargement. The reduction in prostate size and associated symptom relief, therefore, takes some time.
81
# Which of the following anti-epileptics are most assoc weight gain Ethosuximide Sodium valproate Levetiracetam Carbamazepine Lamotrigine
Sodium valproate
82
Drugs that cause raised prolactin
phenothiazines, metoclopramide, domperidone
83
IgG | 75%
Enhances phagocytosis of bacteria and viruses Fixes complement and passes to the fetal circulation Most abundant isotype in blood serum
84
IgA | 15%
Predominant immunoglobulin in breast milk Found in secretions of digestive, respiratory, and urogenital tracts Provides localized protection on mucous membranes Most commonly produced immunoglobulin in the body (lower blood serum concentrations than IgG) Transported across the interior of the cell via transcytosis
85
IgM | 10% frequency
First immunoglobulins to be secreted in response to an infection Fixes complement but does not pass to the fetal circulation Anti-A, B blood antibodies (pentamer when secreted) Note: Cannot pass to the fetal circulation, preventing haemolysis
86
IgD | 1%
Role in immune system largely unknown Involved in activation of B cells
87
IgE | 0.1%
Mediates type 1 hypersensitivity reactions Synthesized by plasma cells Binds to Fc receptors on mast cells and basophils Provides immunity to parasites like helminths Least abundant isotype in blood serum
88
# Drugs causing ocular problems Cataracts Corneal opacities | Cataracts - clouding of lens
Cataracts * steroids Corneal opacities * amiodarone * indomethacin
89
# Drugs causing ocular problems Optic neuritis
ethambutol amiodarone metronidazole
90
# Drugs causing ocular problems Retinopathy
chloroquine, quinine
91
# Drugs causing ocular problems What does sildenafil cause?
Sildenafil can cause both blue discolouration and non-arteritic anterior ischaemic neuropathy
92
# Interferon Interferon Alpha uses
produced by leucocytes antiviral action useful in hepatitis B & C, Kaposi's sarcoma, metastatic renal cell cancer, hairy cell leukaemia adverse effects include flu-like symptoms and depression
93
Interferon beta
produced by fibroblasts antiviral action reduces the frequency of exacerbations in patients with relapsing-remitting MS
94
Interferon gamma
predominately natural killer cells. Also by T helper cells weaker antiviral action, more of a role in immunomodulation particularly macrophage activation may be useful in chronic granulomatous disease and osteopetrosis
95
# Immunology What would be the difference in results of Immunoglobulin electrophoresis for multiple myeloma vs waldenstroms
IgM paraproteinemia points to Waldenstroms Monoclonal IgG OR IgA will be raised in MM
96
Which one of the following is contraindicated in ischaemic heart disease and chronic heart failure? Amiodarone, digoxin, bisoprolol, flecainide, warfarin
Flecainide - class IC anti-arrhythmic is associated with increased risk of arrhythmia (it slows down conduction of APs)
97
Recommend Adult Life Support (ALS) adrenaline doses for anaphylaxis vs cardiac arrest
anaphylaxis: 0.5mg - 0.5ml 1:1,000 IM cardiac arrest: 1mg - 10ml 1:10,000 IV or 1ml of 1:1000 IV

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