Pharmacology+perscriptions Flashcards
What is ‘indication’
use of that drug for treating a particular disease
What is a ‘contracindication’
Specific situation in which a drug, procedure or surgery should not be used as it may become harmful
ACEi hypertension
Common examples: ramipril, lisinopril, enalapril
Mechanism of action: work on the renin-angiotensin system, reducing the formation of angiotensin 2 (a vasoconstrictor) which in turn causes vasodilation. Conversely, they also increase the formation of bradykinin, a peptide which is a vasodilator.
Have renal-protective effects, which is why they are always preferred first line for patients with Type 1 diabetes
Ramipril hypertension
ACEi drug
Dose range for hypertension: 1.25-10mg once daily
10% patients will develop dry cough due to increased bradkykinins – manage appropriately
Cautions (i.e. things to look out for/circumstances in which the medicine can be used but cautiously and with increased monitoring): diabetes (may lower blood glucose); first dose hypotension
Contraindications:
Common/key side effects: alopecia, angina pectoris, angioedema (more common in Afro-Carribean patients), constipation, dry cough, electrolyte imbalance (INCREASE potassium, DECREASE sodium)
Key point for practice: around 10% of patients will develop a dry cough (due to bradykinin), so please be on the lookout for this in patients who are newly prescribed an ACE inhibitor, but also those who have been prescribed it for a while as the cause of a cough may have been missed
A2RB hypertension
Common examples: losartan, candesartan, irbesartan
Mechanism of action: reversibly and competitively prevents angiotensin II binding to the AT1 receptor in smooth muscle and other tissues. This leads to relaxation of the smooth muscle, reducing blood pressure.
NOT to be combined with an ACEi in the treatment of hypertension
DOES NOT cause cough (does not increase bradykinin levels which is the cause of cough when using ACEi)
Losartan potassium (hypertension)
A2RB drug
Dose range for hypertension: 50-100mg
Cautions: Afro-Carribean patients (reduced benefit), elderly (use lower doses initially), renal artery stenosis
Contraindications: NOT to be given with the drug ‘aliskiren’ in patients with an estimated Glomerular Filtration Rate (renal function measure) of <60mL/minute or those with diabetes
Common/key side effects: abdominal pain, cough, diarrhoea, postural hypotension (more common in those also taking diuretics)
Key point for practice: the ‘potassium’ given after the drug name is the ‘drug salt’. Often drugs are formulated with another molecule to increase their solubility.
Calcium channel blockers for hypertension (Dihydropyridines)
Common examples: amlodipine, felodipine, lercanidipine, nifedipine
Mechanism of action: peripheral arterial vasodilators that work by blocking calcium influx into vascular smooth muscle (and less so cardiac muscle), which in turn reduces contraction of those muscles as cells are dependent on extracellular movement of calcium ions
Amlodipine for hypertension
Ca channel blocker (CCB)
Dose range for hypertension: 5-10mg once daily
Cautions: elderly
Contraindications: cardiogenic shock, significant aortic stenosis, unstable angina
Common/key side effects: abdominal pain, dizziness, drowsiness
Key point for practice: if a patient is recently started on amlodipine and suffers ankle swelling, the drug is the likely cause – although not always!
Thiazide diuretics
Common example: Bendroflumethiazide, indapamide (‘thiazide-like’)
Mechanism of action: inhibits sodium and chloride ion reabsorption from the distal convoluted tubules in the kidneys. Water follows ions (movement from high to low water potential) and therefore this ion movement causes increased water loss, increasing how often patients urinate. It also has an effect on vascular smooth muscle, where it is thought to dilate blood vessels.
Most hypertensive drugs cause electrolyte imbalance – thiazide decrease K+ and acei decrease K+
Bendroflumethiazide hypertenison
Thiazide drug
Dose range for hypertension: 5-10mg daily (maintenance dose)
Cautions: diabetes, gout, hyperaldosteronism, malnourishment, nephrotic syndrome, systemic lupus, elderly (use lower doses)
Common/key side effects: alkalosis hypochloraemic, constipation, diarrhoea, electrolyte imbalance (hypokalaemia in particular!)
Beta blockers hypertension
Common example: propranolol, atenolol, bisoprolol, labetalol
Mechanism of action: through action at beta-adrenergic receptors, either prevent increases in heart rate or prevent contraction of vascular smooth muscle
Some beta-blockers are classed as ‘cardioselective’; meaning can specifically target receptors in the heart
Atenolol
B blocker drug
Dose range for hypertension: 25-50mg daily
Cautions: diabetes (masks hypoglycaemic symptoms!), first-degree AV blockm, history of obstructive airway disease (can use but cautiously)
Contraindications: asthma, cardiogenic shock,
Common/key side effects: bradycardia, depression, dry eye, fatigue, peripheral coldness (due to vasoconstriction), sleep disorders
Key point for practice: we avoid beta-blockers in asthmatic patients or those with a history of bronchospasm as they cause bronchoconstriction (beta receptor action)
Statins
Common examples: simvastatin, atorvastatin, rosuvastatin
Mechanism of action: competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, an enzyme involved in cholesterol synthesis in the Liver
Myopathy (muscle toxicity) can occur with any statin and be incredibly painful and dehabilitating. Statin therapy is typically not started if the baseline creatine kinase concentration (biproduct of muscle cell turnover) is more than 5 times the upper limit of normal.
If already started treatment, if symptoms are severe discontinue (ezetimibe can be tried instead) and if creatinine kinase markedly raised then also discontinue
Simvastatin
Statin
Dose range for hypertension: 10-80mg daily at night
Cautions: elderly, high alcohol intake, history of liver disease, hypothyroidism
Common/key side effects: asthenia, constipation, dizziness, myopathy
Key point for practice: 10mg tablets can actually be purchased from a pharmacy without prescription (as a ‘Pharmacy’ medicine)
Atrovastatin
Statin
Dose range for hypertension: 10-80mg daily
Cautions: elderly, high alcohol intake, history of liver disease, hyperthyroidism
Common/key side effects: asthenia, constipation, dizziness and myopathy
Key point for practice: unlike simvastatin, the dose does not have to be taken at night although many clinicians believe it does
modified release tablets
Used where the rapid onset of a drug is not desirable or a delay is sought
The dosage form is changed so to modify the drug release profile
There are two types:
Delayed-release e.g. gastro-resistant (enteric) tablets. The drug is released at a predefined time or in a particular area of the gastrointestinal tract
Extended-release (also known as prolonged or sustained release tablets). The drug is released more slowly over a longer period, which in turn sustains drug plasma levels
Oral administration advantages and disadvantages
Advantages:
Patient preference (painless, easy, portable)
Cheap (to both manufacture and administer)
Variety of dosage forms available
High dose is possible
Can use modified release approaches
Disadvantages:
Extensive first-pass metabolism, which may require large doses to achieve the desired therapeutic effect
Food effects
Not suitable for particular patients e.g. unconscious
Drug delivery via topical patches
Transdermal patches deliver a constant and controlled dosage
Advantages:
Avoid pH variations of the GI tract
Avoid majority of first-pass metabolism
Disadvantages:
Few drugs are suitable for transdermal delivery
topical drug administration advantages and disadvantages
Advantages: Patient preference (easy, but sometimes messy e.g. ointments) Avoid pH variations of the GI tract Avoid majority of first-pass metabolism Stop absorption
Disadvantages:
Few drugs are suitable for transdermal delivery
Slow absorption
Parenteral administration
Technically, any method of drug administration that does not involve the gastrointestinal tract (enteral route); however, in practice, the term is used for administration methods via injection for example: Intravenous (also infusions) Intramuscular Subcutaneous Intra-articular Intradermal Intraspinal/intrathecal (never vinca-alkaloids e.g. vincristine & vinblastine!) Intra-arterial
types of perscription
NHS prescriptions (medicines that most patients do not pay for) FP10 – green FP10MDA – blue FP10D – yellow FP10PN and FP10SP – lilac Hospital drug charts
Private prescriptions (medicines that patients always pay for)
These can be written on anything deemed suitable by the supplying pharmacist e.g. plain white paper
FP10PCD – pink – private prescriptions for controlled drugs
Drug information included on perscription
Name of drug Dose regimen (eg 1 tablet taken daily) Quantity given Formlation eg tablets Strength
unlicensed meds
By law, before a medicine can be placed on the market, it must be given a marketing authorisation (product license) by a medicines regulator (the MHRA in the UK)
Unlicensed medicines are:
Medicines which have a license in other countries but not in the UK, so are imported
Medicines which have a UK license but need to be made up into another formulation which has no license
A medicine that has no license at all, anywhere
off label med use
If a medicine is prescribed or used ‘off-label’, this means that the medicine is being used in a different way than that described in the UK marketing authorisation (product license); for example:
Using a medicine for a different indication (condition) than that stated in its license
Using a medicine in an age group outside the licensed range
Using a medicine at a higher dose than stated in the license
Adverse drug reactions
Type A: augmented reactions result from exaggeration of drugs normal pharmalogical actions when given at usual dose
Type B: bizarre reactions unexpected of drugs actions
Type C: continuing reactions persistent for long time
Type D: delayed reactions apparent some time after medicine use
Type E: end-of-use reactions associated with withdrawals
MI immediate management
300mg loading dose aspirin/clopidogrel
continue at 75mg for up to 12 months
aspirin
Mechanism of action: COX-1 inhibitor which interferes with thromboxane A2 in platelets, preventing platelet aggregation
Formulation: tablets
Dose range post NSTEMI: 75mg – 300mg
Key practice point: someone with a suspected ACS should chew aspirin immediately if available to them
usually put on aspirin for life
clopidogrel
Mechanism of action: binds to ADP receptors on platelets, preventing the platelet aggregation cascade
Formulation: tablets
Dose range: 75mg – 300mg
Key practice point: a similar drug to aspirin, clopidogrel can be given as monotherapy post NSTEMI if aspirin is contraindicated
also given up to 12 months post event
NSTEMI/unstable angina drugs
aspirin/clopidogrel
Nitrates are used for pain, as they dilate coronary blood vessels
Patients should also be given an anticoagulant such as heparin or low molecular weight heparin or fondaparinux
Beta-blockers can also offer benefit and should be continued indefinitely
A glycoprotein Iib/IIIa inhibitor such as eptifibatide can be given alongside the anticoagulant/antiplatelet in patients at high risk of death. This can also be given to those undergoing PCI
ACE inhibitors for left ventricular systolic dysfunction
statins to reduce risk of recurrent MI, CAD and need for revascularisation and stroke risk
Nitrates
nitrates are used for pain relief. They dilate the coronary blood vessels, relieving tightness in the chest
Patients will be provided with a glyceryl trinitrate (GTN) spray post NSTEMI, which they spray sublingually for quick absorption of the drug and relief of chest tightness
Other formulations include tablets (isosorbide mononitrate), and sometimes isosorbide dinitrate is given intravenously if the spray is not effective at relieving pain
Many ACS patients continue to use the sublingual GTN spray for ongoing relief of chest pain/tightness. As nitrates dilate blood vessels, they commonly cause headaches and so patients should be made aware of this.
Heparins
Mechanism of action: inhibit to action of various clotting factors e.g. enoxaparin (a low molecular weight heparin) works to inhibit factor Xa
Heparin and low molecular weight heparins (LMWH)
Fondaparinux is slightly different to heparin/LMWH,
glycoprotein IIb/IIIa inhbitor
Most common example: eptifibatide
Mechanism of action: reversibly binds to the platelet receptor glycoprotein Iib/IIIa preventing the binding of fibrinogen, VWF and other molecules which lead to platelet adhesion
types of drug interactions
drug-drug: benefical or adverse phamacodynamics
drug-disease: aspirin use in gout patients
drug-alcohol: can induce or inhibit enzymes, increases effect with depressants
drug-food: often caused by enzyme interactions
drug-labatory: changes laboratory test
polypharmacy
concomitant of more than 5 drugs
excessive polypharmacy is more than 10 drugs
Rhythm control(AF) flecainide
dose for cardioversion: 50-300mg daily
Specific monitoring: regular ECGs one week after starting then after dose changes
side effects: visual disturbance, GI smptoms
blocks Na channels slowing conduction and HR
most common therapeutic choice
often better tolerated than other antiarrythmic drugs
only used for those with no cardiac defects
Rhythm control AF amiodarone hydrochloride
dose: 200mg TDS (3x daily) for one week then 200mg BD (2x daily) then 200mg OD (once daily) continuously or lowest dose needed to control arrhythmia
Specific monitoring: TFTs and LFTs before and every 6 months after
serum potassium before and CXR
side effects: corneal microdepositis, thyroid function derangement, hepatotoxicity, pulmonary toxicity
works by blocking potassium channels slowing HR prolonging each AP
contraindications: severe conduction disturbance, sinus node disease, sinus bradycardia, thyroid dysfunction
Rhythm control AF sotalol
As well as slowing the heart (rate control), sotalol also is a type II/III anti-arrhythmic. The latter properties come at higher doses. Mechanism is similar to amiodarone, by blocking potassium channels to slow cardiac conduction
Dose (for cardioversion): initially 80mg in divided doses, increased to 160-320mg daily divided doses, gradual increase at intervals of 2-3days
Specific monitoring: regular ECGs (every week and after dose change). Can actually cause arrythmias so monitoring is crucial.
Side effects: bradycardia, fatigue, cold extremities, light-headedness
contraindications: asthma, cardiogenic shock, hypotension, metabolic acidosis, prinzmetals angina, 2nd degree block, severe PAD, sick sinus syndrome, 3rd degree block, uncontrolled HF
Warfarin
A Vitamin K antagonist which prevents the reduction of Vitamin K which is needed to make clotting factors; fewer clotting factors = increased time to clot
dose by mouth; initially 5-10mg day 1. subsequent doses depend on prothrombin time (measured by INR grading and by time in therapeutic range)
lower dose given over 3-4weeks in non-rapid cases
elderly patients given 3-9mg daily
interactions: foods high in vitamin K or supplements, alcohol interaction effect on liver
side effects: haemorrhage, alopecia, nausea, vomiting
contraindications: post 48hrs of haemorrhagic stroke
NOACS for AF
Novel Oral Anticoagulant Drugs (‘NOACS’)
These directly inhibit a particular clotting factor rather than have a wide ranging effect on other clotting factors. Bleed risk is therefore lower – although there IS still a bleed risk. They can only be used in NON-VALVULAR AF, where valve involvement warfarin is used.
licensed for AF:
- apixaban
- dabigatran
- rivaroxaban
clear indications for use eg dabigatran required LVEF of less than 40%
Apixaban tablets
Direct inhibitor of Factor Xa
Dosed TWICE daily, whereas rivaroxaban is only once daily. This requires patients remember to take two doses a day rather than one.
Dose adjustment in renal impairment
MHRA advice (2019): increased risk of thrombotic events in patients with antiphospholipid syndrome and a history of thrombosis. MHRA advice (2020): reminder of bleed risk and reversal agents
Dabigatran capsules
Direct inhibitor of thrombin
Has the greatest number of product licenses of the NOACs (i.e. AF but also many other indications)
Dosed TWICE daily, whereas rivaroxaban is only once daily. This requires patients remember to take two doses a day rather than one.
Dose adjustment in renal impairment
MHRA advice from previous slide applies here, too
Side effects: abnormal hepatic function, anaemia, diarrhoea, haemorrhage
Rivaroxaban tablets
Direct inhibitor of Factor Xa
The first NOAC to market
MUST be taken with food
Dosed ONCE daily
Dose adjustment in renal impairment
MHRA advice from previous slide applies here, too
Side effects: anaemia, constipation, haemorrhage
