Pharmo Flashcards
Yellow card
Black triangle = all
Established - serious
Paediatir= all
Legal requirements prescribing
Legible ink
2 ID
signed dated
Define slip, lapse, mistake, volation
Concentration
Memory
Knowledge
Intentional
First pass metb includes
Liver, gut wall and gut lumen
Describe protein binding of different drugs
Albumin = acidic drugs
Globulins = hormones
Lipoproteins = basic drugs
Acid glycoproteins = basic drugs
What is Vd affected by?
Receptor sites in tissues Regional blood flow Lipid solubility Active transport Disease DDIs
CYP inducers
Phenytoin Carbamazepine Barbiturates Rifamipicin Alocohol (chronic St John's Wort
CYP inhibitors
Omeprazole Disulphram Erythromycin/Macrolides Valporate Isoniazid Cimetidine Ethanol (acute) Sulphonylureas Grapefruit juiceCranberry Antifungles
Hepatic disease (opiates in cirrhosis)
When should you monitor drugs?
Long half life
Narrow TI
Risk of DDIS
0 order
What does BNF contain
Comprehensive list of all licensed drugs in the UK
Role of pharmacist in prescribing
No legal responsibility
Check prescriptions are correct
Pharmokinetics of Digoxin
Long half life = 40hrs
Narrow Ti
builds up in renal failure
Large Vd
How do you calculate Loading dose
Vd x [Drug at target}
Note that Vd = L or L/kg
How do you calculate the elimination rate constant?
=slope of the curve (k)
= clearance/Vd
Calculation of T1/2
Vd (kg)/Cl log0.5/k
T1/2 in children
Higher as Vd is lower as more of their body is ECF
Comptments and drugs
Equilibrium in each compartment.
Varies
Describe drug specificity and selectivity
The more selective the less undesired effects elsewhere. Affinity for one receptor over another.
The more specific the more it can be used for a select organ. Specific basically means its so selective that no matter how much you give it wont work at another site
DDI absorption example
Gastric emptying - metaclopramide. Affects Fe and tetracyline absorption
Types of ADRs
A= augmented effect (dose)
B = Unpredicable off target
C = chronic
D = Delayed e.g. osteoporosis and steroids
E = End of treatment effects
Mild, moderate(additional treatment) or major
Preparations of testosterone?
Oral, IM, implant
Steroid hormones and distribution?
Steroid hormone binding globulin (not prog) and albumin
Use/ Actions of ostradiol
Prevent HRT symptoms - hot flushes, support bone structure. Anabolic Na/H2O retention Impair glucose tolerance Increase coagubility Improves mood and concentration
Side effects of oestradiol
Water retention N/V Diabetes Breast tenderness Thromboembolism Endometrial hyperplasia and cancer
Actions of prog
Anabolic Increase Bone density Secretory to endometrium Fluid retention Mood changes
Side effects of Prof
Water retention Depression (PMS) Irritability Weight gain Acne N/V Lack of conc
Actions/ Side effects of testosterone
Male secondary sexual characteristics Anabolic Acne voice change Aggression Metabolic adverse effect on lipids - increases LDL and decreases HDL
Preparations of COCP?
Monophasic
Triphasic
How does COCP work?
Suppresses ovulation (inhibit LH and FSH), effect on mucus and endometrium
MEtabolism of COCP?
CYP
Absorption of COCP DDI?
Broad spec on flora
Some COCP ADRS
Focal migranes (stroke) Headache Moodswing Gall stones Precipitate porphyria (skin sensitivity-dark urine-memntal disturb) weight gain
Use of POP?
Not as effective
Action on Cervical mucus and endometrium
Emergency contraception (72hrs) (120?)
Cu IUD - 5 days
Formulation of HRT?
Sequential or continuous
No shedding in continuous (Cx?)
Treat with lowest dose for shortest time
ADRs of HRT
Breast cancer Endometrial cancer IHD DVT Uterine bleeding Lipid profile Thrombophilia
Anti-oestrogens and action e.g. tamoxifen/ Clomiphene
Weak oestrogens - block receptors.
Induce ovulation by blocking oestrogen affect on put. More GnRH
Tamoxifen also acts at bone. Used in breast cancer.
Better for HRT as can reduce cancer risk, not be proliferative. But can increase hot flushes
Affects of anti-progs
Partial agonist again.
Sensitises uterus to prostaglandins (like increased O:P0)
Induction of labur
Terminaton of pregnancy
Effect of high LDL?
Pro atherogenic
Toxic to endothelial. enhance platelet aggregation.
Affect of obesity on lipid profile
Increases Cholesterol, Triglycerices and decreases HDL
Action of simvastatin/ atorvastatin
Inhibit HMGCoA reductase
Used in CVS risk and hypercholesterolaemia
Decrease VLDL and LDL.
Anti-inflammatory, plaque reduction, improved endothelial cell function, reduce thrombotic risk, slow neurodegeneration.
ADR of simvastatin/ atorvastatin
LFTS (reversible)
Myopathy - CPK
Metab and elimination of Statins DDIS
CYP
OATP2 - fibrates and cyclosporin augment affect
Describe Benzafibrates action
PPARalpha agonist. More lipoprotein lipase Reduce TG (espc Post prandial) Not great LDL decrease Increase LDL size Increase HDL-C
ADRs Benzafibrates
Rhabdomolitis
Myopathy
LFTs
Nicotinic acid action
Reduces VLDL
Increase HDL (best C)
Inhibits lipoprotein synthesis.
Reduce coronary events
ADRS/ contraindications for Nicotinic acid
Flushing, itching, headache Hepatotoxicity GI Peptic ulcer hyperglycaemia CIs: Liver, PUD
Ezetimibe action and uses
Cholesterol absorption. Circulates enterohepatically. Lowers LDL (more hepatic receptors)
ADRs of Ezetimibe
Headache, abdo pain, diarrhoea
Give a statin?
CVS risk tables in BNF
MoA metformin
Decrease insulin resistance and hepatic glucose production
Side effects metformin
GI
Lactic acidosis (HRH)
Vit B 12 deficiency
No weight gain/hypos
MoA Gliclazide
Increase production
K/ATP channel antagonist
Increase Ca release
ADR sulphonylurea
Weight gain
Hypo
Pioglatizone Rosiglatizone MoA
PPAR receptor. Decrease FAs. Increased muscle and adipose sensitivity
Pioglatizone Rosiglatizone ADRs
Bladder cancer Fluid retention and CVS risk Osteoporosis No hypos More LDL and HDL
Repaglinide, Nateglinide MoA
K/ATP antagonist
Repaglinide, Nateglinide ADRs
Hypo (lower risk)
No Weight gain
Repaglinide, Nateglinide pharmacokinetics
Short half life so taken before meals
DPP4 inhibits/ GLP1 analogue
Integrinpathway
GLP released from distension of the stomach.
DPP4 breaks down GLP.
GLP increases insulin secretion and suppresses appetite
GLP1 agonist more effective
GLP1/ DPP4 inhibitor ADRs
N/V
Diarrhoea
GORD
Injected so pain
SGLT2 inhibitor action
Blocks in PCT
SGLT2 ADRs
Polyurea
Polydipsia
Thrush
UTI
Acarbose/ a-glcosidase inhibitors ADRs
Flatulence
Diarrhoea
Criteria for treatment of Diab?
over 7% = sulphonylureas
over 7.5 = TZD or 3rd drug
Insulin (titrated upwards)
Physiological effects of Insulin
Glucose uptake in liver, muscle, adipose Glycogesis in liver Lipogenesis in Adiposites Proteogensis in Muscle cells Inhibit gluconeogensis
Half live of insulin
5 mins
Best indulin regime
Long acting with rapid acting`
Types of insulins
Animal porcine and bovine
Short acting
30-60mins.
Given 15-30 preprandial
Peaks at 2 hours
Examples of short acting insulins
Actrapid, Humulin , Novorapid
Examples of longer acting insulins
Insulin Glargine
Rapid acting insulins
onset 5-15
Inject prandial
Peaks at 30-90
lasts 4-6
Intermediate acting inslins
Isophane intermediate actin (NPH)/ Humulin I.
Onset 1.5-3, peaks at 4-8. lasts 12-20.
Long acting basal analogue insulins
Slow onset 2-6hours, duration up to 24
Very long acting insulins
Fatty acid added so longer into blood stream. Lasts up to 50 hours (glargine)
ADRs inslin
Hyper/hypos
Lipodystrophy
Painful injection site
Insulin allergy
Sources of insulin error
Programme not written up
Name of insulin incorrect
Number/ dose unclear
Unit unclear
MoA orlistat
Gastric and pancreatic lipase inhibitor. FA conversion decreased by 30%. Needs to be combined with diet
ADRs orlistat
Soft, fatty stools, risk of flatus, faecal incontinence
What is pharmacovigilance
Process of identifying and then responding to safety issues about marketed drugs. Ensure saftey Minise risk Optimise benefit Withdrawral of drug results? (E)
Aims of pharmacovigilance
ID unrecognised safety hazards and quantify
Factors predisposing toxicity
Evidence for safety
False positive ADR
Why is pharmacovigilence needed?
PAtients in trials are restricted Limited duration of drugs Specialists giving drugs in trials Different monitoring Not big enough sample
How are ADRs identified?
Spontaneously reported to the MHRA - Medicines and healthcare products regulatory agency. through yellow card. (licencing responsibility. Can report to pharmacological company (post marketing surveillance).
Cohort or case control
Advantages of spontaneous reporting
Involves all Everything included IInexpensive Continuous Can generate ADR hypothesis ID risk factors
Limitations of spontaneous reporting
Undereporting Delay in reorting Misleading information given No control group Cant get incidence rate as no idea how many are treated
Controvosy in yellow card
Quality of patient reports?
Under reporting
Difference between pharmacogenetics vs genomics
Gene vs entire genome
Variability in ADRs. drugs
Some toxic, some not
Some effective some non responders.
Particulary CYP
Variability in ACEi
Better for whites as they have a higher RAS activity
Older and afrocarribean = CCB
Issues surrounding pharmacogenetics
DNA database
Synthetic cortisol
Hydrocortisone
Prednisolone also a glucocorticoid
More potent than cortisol?
Dexamethasone
Metabolic actions of glucocorticoids
Glycogenolysis Gluconeogenesis Hyperglycaemia Proteinolysis Lipolysis (low/physiological) Lipogenesis (high) Redistricubution of fat centrally Slight mineralocorticoid activity
Mineralocorticoid deficiency and example
Fludrocortisone (a bit at GC) Hyponatraemia Dehydration Hypotension Hyperkalaemia
Actions of hydrocortisone
Prednisolone
Dexamethasone, Betamethasone, fludrocortisone at GC and MC
GC MC HC equal Pred more at GC Dex and Bet +++GC no MC Fludo --GC, +++MC
Pharmacokinetics of corticosteroids
All have high bioav All metabolised in liver 1 & 2 Glucoronidation in liver for stage 2 Clearance affected by age Kidney can metabolise too
Steroid action on immune repsonse
Inhibit B, T, cytokines, cell adhesion molecules, phagocytes
MoA steroids
Steroid receptor (HSP dissociated)
Bind to hormone response element (HRE/ GRE) on DNA
Activates/ inhibits transcription = transactivation/ cis repression.
Transactivation = antiinflam
Cis repression = keratin, oesteo, POMC (side effects)
Trans repression (protein) = immune/ cytoknes
Some non genomic MoA via surface receptors
Some glucoorticoid ADRs
Adrenal crisis - hypogly, shock/ hypotension/ hypokalaemia/ hyponatraemia/ dehydration Inhbits osteoblast, ca absorption. PUD hypertension DM Catacts Psychosis
Describe influenza A,B,C
A = Multiple host species, most severe, various. B = No animal reservoir, lower mortality C = not clinically important
Amantadine and Rimantadine MoA
Block M2 channel and inhibit uncoating. Proton channel that allows A to enter.
Highly resistant
ADR amantadine and rimantadine
CNS nervousness, anxiety, agitation, insomnia think schitzo as similar to anticyclic
Give examples of neuroaminidase targetting drugs
Oseltamivir (Tamiflu) and Zanamivir
MoA of neuroaminidase targeting drugs
Neuroaminidase removes sialic acid bridges between virus particles so that particles can be exocytoses.
Blocking causes aggregation.
Earlier treatment the better.
High resistance - monitored by WHO
ADRs of neuroaminidase inhibitors
Vomiting, abdo pain, epistaxis.
Resp depression, bronchospasm
Folic acid antibitic examples and action
DNA synthesis
Trimethoprin and sulphonamides
What is an E test?
Sensitivity testing. Measures the minimum inhibitory concentration
What is the MIH?
The minimum concentration of antibiotic required to inhibt growth of a bacterium in vitro (mg/l). Antibiotic and isolate specific.
What are breakpoints?
Clinical testing data, wild type MIC, and antibiotic pharmacokinetics calulate breakponts. Susceptibile Intermediate Resistnt. Compare with MIC
Drug is effective when in microbiological terms?
Maximal concentration (Cmax) and MIC ratio.
MoA of antibiotics in terms of dependent killing
Time dependent killing - porlonged no at high conc e.g. beta lactams and glyco.
Concentration dependent killing e.g. aminoglycosides and quinolones
describe MDR, XDR PDR
MDR - Non-susceptibility to at least one agent in 3 or more categories
XDR NS to at least… in all but two or fewer
PDR
All microbial categories
ADR penicillin
Hypersensitivity, CNS
Cephalosportin ADR
Hypersensitity, C diff
Tetracylins ADr
N/V/D
Aminoglycosies ADR
Renal and ototoxicity
ADR Macrolides
N/V/D
ADR Cloramphenical and MoA
Broad spec, protein
BM
Liver toxicity
Glycopeptides
Renal, Bone marrow, ototoxoicity
Drugs that are monitored
Vancomysin and aminoglycosides.
Monitor FBC for clor
Renal and aud for gent
Common DDIs for antibiotics
Anticoag
Antiepileptics and carbapenems
Bisphosphonates (hypocal) and aminohlycosides
Digoxin in amino
Digoxin ADRs
blurred vision, confusion, drowsiness, dizziness, depression, psychosis, convulsions
Describe RA
Autoimmune
Common 1%
Initially localised to synovium
Inflammatory change and proliferation leading to destruction of cart and bone
How is RA diagnosed
Clinically Morning stiffness >3 joints (often hand) Symmetrical Rheumatoid nodules (ripe fruit) Serum factor X ray (only late stage)
Describe SLE/ Vasculitis
Necrosis of distal vessels
Skin rash
Granulomatosis with certain types
What are DMARDs
Disease modifying antirheumatic drugs
Lead to clinical improvement unlike NSAIDs.
Azathioprine MoA
Active metabolite = 6MP (Mercaptopurine)
Decreases DNA and RNA synthesis.
TMPT metabolises but varying rate. Low rates = myelosuppression
Use of Azathioprine
Transplants SLE/ Vasc Weak for RA IBD Bullous skin disease Atropic dermatitis Steroid sparing drug
ADRs Azathioprine
BM suppression
non hodgkin lymphoma
Infection
Hepatitis
Cacineurin inhibitors e.g. ciclosporin and Tacrolimys MoA
Against T helper cells and IL2
Cyclophilin protein/ TBP.
IL2 regulates WBCs
Cacineurin inhibitors e.g. ciclosporin and Tacrolimys ADRsa
eGFR - nephrotoxic BP - hypertension Gingival hyperplasia Hyperlipidaemia N/V/D CYP Does not supress bone marrow
Uses of Cacineurin inhibitors e.g. ciclosporin and Tacrolimys
Transplants
Dermatis and psoriasis
Mycophenolate Mofetil (MMF) MoA
Inhibits monophosphate dehydrogenase and therefore guanosine synthesis.
Inhibits B/T cell proliferation. but highly selective
Uses Mycophenolate Mofetil (MMF)
Transplants
SLE
Monitor metabolite
Mycophenolate Mofetil (MMF) ADRs
N/V
Myelosuppression
Liver and kidney disease
Viral infection
Methotrexate MoA
Inhibits dihydrofolate reductase and purine and thymidine synhesis (malignant only).
In RA - inhibits T cells, cell adhesion and adenosine
Uses MTX
RA
Psoriasis
Crohns
Pharmokinetics MTX
One a week Long half life Low bioavailability Highly bound - NSAIDs Renal excretion
ADRs MTX
Nausea Mucositis BM (give folic acid) Hepatits/ cirrhosis Pneumonitis Tetratogen Abortifacient
Do baseline CXR, FBC, LFT, UE, Creatine
Sulphasalazine/ Masalazine MoA
Inhibit T cell proliferation and IL2
Inhibit neutrophil
Uses of sulphasalazine/ masalazine
RA
Chrons
UC
ADRs of sulphasalazine
Safe in preg Hepatits Rash ASprin reaction N/V/ abdopain
AntiTNF e.g. infliximab MoA
Inhibits cytokine cascade- adhesion, recruitment, less angiogenesis, less joint destruction e.g. MMP
USes infliximab
Expensive so other DMARD must have been tried. Withdrawn if no effect in 6 months or any ADR.
RA
IBD
ADRs Infliximab
Viral infection
TB
Rituximab MoA
Targets CD20 B cells. Induces apoptosis.
Uses Rituximab
RA, especially with MTX
ADRs Rituximab
Hypergammaglobulinaemia
Hypersensitivity
Cyclophosphamide MoA
Alkylating - DNA cross links
BM supression
CYP
Kidney
Cyclophosphamide uses
Lymphoma Leukaemia Sipus nephritis Wegners granulomatosis Polyarteritis nodosum Vasculitis
Cyclophosphamide ASDRs
Haemorrhagic cystitis
Bladder cnacer, lymphoma, leukaemia
Hepatitis
Renal impairment
Pathophysiology asthma
TH2 dirven inflammation Airway remodelling Bronchostriction Mucosa oedema Neutrophilic or eosinophilic Mast cells-IgE and leukocytes Bronchospasm and congestion due to epithelial damage, thickening of BM
Basics of asthma treatment
Check compliance, technique
Eliminate triggers
Severe asthma criteria
unable to comple sentences
HR >110
RR>25 PF 33-50% of best
Life threatening asthma
If severe plus
PEF
Near fatal asthma
PaCo2 >6 = mechanical ventilation