Clinical Pharmacology Flashcards
Acute intermittent porphyria
What drugs may precipitate attack?
AIP is caused by defect in porphobilinogen deaminase
Drugs which may precipitate attack in AIP
* barbiturates
* halothane
* benzodiazepines
* alcohol
* oral contraceptive pill
* sulphonamides
What is the effect of adrenaline?
Sympathomimetic amine - has both alpha + beta adernergic stim properties
- 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
Give an example of beta1 and beta2 agonists
Beta-1 agonists
dobutamine
Beta-2 agonists
salbutamol
Give an example of alpha 1 and 2 agonists
Alpha-1 agonists
phenylephrine
Alpha-2 agonists
clonidine
Adrenoreceptor antagonists
Alpha-1 antagonist
Alpha-1a antagonist
Alpha-2 antagonist
Alpha antagonists
alpha-1: doxazosin
alpha-1a: tamsulosin - acts mainly on urogenital tract
alpha-2: yohimbine
Name a beta-1 antagonist and non-selective antagonist
Beta antagonists
beta-1: atenolol
non-selective: propranolol
Allopurinol interactions
- Azathioprine
- Cyclophosphamide - reduced renal clearance, marrow toxicity
- Theophylline - increase plasma concentration
Describe the mechanism by which amiodarone causes hypothyroidism
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
Beta-blocker overdose
Features
Management
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
Ciclosporin
nephrotoxicity
hepatotoxicity
fluid retention
hypertension
hyperkalaemia
hypertrichosis
gingival hyperplasia
tremor
impaired glucose tolerance
hyperlipidaemia
increased susceptibility to severe infection
Digoxin
MOA
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
Digoxin toxicity
Features
Features
* generally unwell, lethargy, nausea & vomiting, anorexia, confusion, yellow-green vision
* arrhythmias (e.g. AV block, bradycardia)
* gynaecomastia
Why is hypokalaemia a precipitating factor of digoxin toxicity
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
Management of digoxin toxicity
Management
Digibind
correct arrhythmias
monitor potassium
Drugs that cause impaired glucose tolerance
thiazides, furosemide (less common)
steroids
tacrolimus, ciclosporin
interferon-alpha
nicotinic acid
antipsychotics
Drug induced thrombocytopenia
quinine
abciximab
NSAIDs
diuretics: furosemide
antibiotics: penicillins, sulphonamides, rifampicin
anticonvulsants: carbamazepine, valproate
heparin
Drugs that cause urinary retention
tricyclic antidepressants e.g. amitriptyline
anticholinergics e.g. antipsychotics, antihistamines
opioids
NSAIDs
disopyramide
Side effects of sulfonylureas
Hypoglycaemic episodes
Increased appetite and weight gain
Syndrome of inappropriate ADH secretion
Liver dysfunction (cholestatic)
Side effects of glitazones
Weight gain
Fluid retention
Liver dysfunction
Fractures
Sife effects of isioniazid
mechanism of action: inhibits mycolic acid synthesis
peripheral neuropathy: prevent with pyridoxine (Vitamin B6)
hepatitis, agranulocytosis
liver enzyme inhibitor
Side effects of pyrazinamide
mechanism of action: converted by pyrazinamidase into pyrazinoic acid which in turn inhibits fatty acid synthase (FAS) I
hyperuricaemia causing gout
arthralgia, myalgia
hepatitis
Ethambutol
Side effect
MOA
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
Cellular targets of drugs
Name 4 main types of cellular targets
- Ligand gated Ion channels
- G-protein coupled receptors
- Tyrosine kinase receptors
- Nuclear receptors
Ligand gated ion channel
Ion channel coupled to a membrane receptor causing direct signalling
Nicotinic acetylcholine receptor
GABA receptor
GPCR
MOA
Eg
- Drug binds to target that causes a sequence of events that leads to indirect signalling cAMP»_space;
- Second messengers cause the effect
- Adrenoreceptors
Tyrosine kinase receptors
MOA
Eg
- When drug activates TKR, leads to phosphorylation that causes cell growth and differentiation
- Insulin
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
Drugs that cause photosensitivity
Causes of drug-induced photosensitivity
thiazides
tetracyclines, sulphonamides, ciprofloxacin
amiodarone
NSAIDs e.g. piroxicam
psoralens
sulphonylureas
Antibiotics
Name bactericidal antibiotic
penicillins
cephalosporins
aminoglycosides
nitrofurantoin
metronidazole
quinolones
rifampicin
isoniazid
Bacteriostatic antibiotics
Name 5
chloramphenicol
macrolides
tetracyclines
sulphonamides
trimethoprim
HIV drugs
What is the mOA of enfuvirtide and maraviroc
Entry inhibitors that prevent HIV-1 from entering and infecting immune cells
HIV management
Name some NRTIs
- Zidovudine
- Abacavir
- Emtricitabine
- Didanosine
- Lamivudine
- Stavudine
- Zalcitabine
- Tenofovir
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
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
What is the MOA of the following drugs
Indinavir, nelfinavir, ritonavir, saquinavir
Side effects
- Protease inhibitors
- indinavir, nelfinavir, ritonavir, saquinavir
- SE: diabetes, cushingoid
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
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
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
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
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
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
Prescribing in renal failure
Drugs to avoid in renal failure
- antibiotics: tetracycline, nitrofurantoin
NSAIDs
lithium
metformin
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.
Antifungals
Azoles
Mechanism of Action: Inhibits 14α-demethylase which produces ergosterol.
Adverse Effects: P450 inhibition, Liver toxicity.
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.
Antifungals
Terbinafine
Mechanism of Action: Inhibits squalene epoxidase.
Adverse Effects: Commonly used in oral form to treat fungal nail infections.
Antifungals
Griseofulvin
Mechanism of Action: Interacts with microtubules to disrupt the mitotic spindle.
Adverse Effects: Induces P450 system, teratogenic.
Antifungals
Flucytosine
Mechanism of Action: Converted by cytosine deaminase to 5-fluorouracil, which inhibits thymidylate synthase and disrupts fungal protein synthesis.
Adverse Effects: Vomiting.
Antifungals
Caspofungin
Mechanism of Action: Inhibits synthesis of beta-glucan, a major fungal cell wall component.
Adverse Effects: Flushing.
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).
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
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)
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
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)
Side effect of finasteride
Works by metaboliseing testosterone
Adverse effects
impotence
decrease libido
ejaculation disorders
gynaecomastia and breast tenderness
drugs causing urticaria
aspirin
penicillins
NSAIDs
opiates
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)
Antiarrhythmics: Vaughan Williams classification
Quinidine
Procainamide
Disopyramide
Class 1a
Block sodium channels
Increases AP duration
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
Antiarrhythmics: Vaughan Williams classification
Lidocaine
Mexiletine
Tocainide
Class 1b
Block sodium channels
Decreases AP duration
Antiarrhythmics: Vaughan Williams classification
Flecainide
Encainide
Propafenone
Class 1c
Block sodium channels
No effect on AP duration
Antiarrhythmics: Vaughan Williams classification
Propranolol
Atenolol
Bisoprolol
Metoprolol
Class II
Beta-adrenoceptor antagonists
Antiarrhythmics: Vaughan Williams classification
Amiodarone
Sotalol
Ibutilide
Bretylium
Class III
Blocks K+ channels
Antiarrhythmics: Vaughan Williams classification
Class IV
Verapamil
Diltiazem
CCB
Management of bulimia
High dose fluoxetine
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
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
Mirabegron
beta 3 agonist
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
Quinine what is a side effect related to the ear?
ototoxicity - tinnitus
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.
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
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
Why cant we just give calcium supplements to CKD patients?
- Alfacidiol is used instead in ESRD
- Does not require activation in kidneys
What antibiotic is associated with skin pigmentation
Minocycline
Drugs causing haemolysis in G6PD
anti-malarials: primaquine
ciprofloxacin
sulph- group drugs: sulphonamides, sulphasalazine, sulfonylureas
Fluconazole and ciclosporin - what is the interaction
Fluconazole inhibits the metabolism of ciclosporin which increases the risk of ciclosporin nephrotoxicity.
MOA of oseltamivir vs aciclovir
Oseltamivir - Neuraminidase inhibitor
Aciclovir - DNA polymerase inhibitor
Aspirin is reversible or non reversible cox inhibitor?
Reversible cox inhibitor
causes anti-platelet effect by its impact on TXA2
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.
Which of the following anti-epileptics are most assoc weight gain
Ethosuximide
Sodium valproate
Levetiracetam
Carbamazepine
Lamotrigine
Sodium valproate
Drugs that cause raised prolactin
phenothiazines, metoclopramide, domperidone
IgG
75%
Enhances phagocytosis of bacteria and viruses
Fixes complement and passes to the fetal circulation
Most abundant isotype in blood serum
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
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
IgD
1%
Role in immune system largely unknown
Involved in activation of B cells
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
Drugs causing ocular problems
Cataracts
Corneal opacities
Cataracts - clouding of lens
Cataracts
* steroids
Corneal opacities
* amiodarone
* indomethacin
Drugs causing ocular problems
Optic neuritis
ethambutol
amiodarone
metronidazole
Drugs causing ocular problems
Retinopathy
chloroquine, quinine
Drugs causing ocular problems
What does sildenafil cause?
Sildenafil can cause both blue discolouration and non-arteritic anterior ischaemic neuropathy
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
Interferon beta
produced by fibroblasts
antiviral action
reduces the frequency of exacerbations in patients with relapsing-remitting MS
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
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
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)
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
