stuff Flashcards
ACEi
lisinopril
ramipril
Limit Angiotensin-I to II by inhibiting ACE
- vasodilation -lower perif resistance -lower afterload
- reduction in aldosterone release - Na and H2O excretion
- reduced ADH release -higher H2O excretion
- bradykinin -vasodilation via NOS/NO and PGI2
*Hypotension dry cough hyperkalaemia renal failure angioedema
X renal artery stenosis, AKD, pregnancy, idiopathic angioedema
! K+ increasing drugs, NSAIDs, other antihypertensives
ARBs
candesartan
losartan
AT1 receptor blocker
No effect on bradykinin
*Hypotension
hyperkalaemia
renal failure
X renal artery stenosis, AKD, pregnancy, (CKD caution)
! K+ increasing drugs, NSAIDs
CCB Dihydropyradine class amlodipine nifedipine nimodipine
stop contraction of smooth muscle
- selective for peripheral vasculature, little chronotropic or inotropic effects
*Ankle swelling
flushing
headaches
palpitations
X unstable angina, severe aortic stenosis
! amlodipine + simvastatin
CCB
Phenylalkyamines
verapamil
Class IV - prolongs action potential/refractory period
less peripheral vasodilation, negative inotropic and chronotropic effects
used for arrhythmia, angina (hypertension)
*Constipation
bradycardia
heart block and cardiac failure
X Poor LV function, AV nodal delay
! Beta blockers, caution with other antihypertensives and antiarrhythmics
CCB
Benzothiazepines
Diltiazem
sit between other CCB classes
Thiazide and thiazide like
Bendroflumethazide
indapamide
Inhibit Na/Cl co-transporter, in distal convoluted tubule
lower Na and H2O reabsorbtion (RAAS compensates with time)
Long term- sensitivity of vascular smooth muscle to vasoconstrictors
Good with oedema
*Hypokalaemia hypernatraemia Hyperuricaemia - gout arrhythmia ^glucose ^cholesterol and triglyceride
X Hypokalaemia, hyponatraemia, gout
! NSAIDs, K+ lowering drugs
Aldosterone receptor antagonist
Spironolactone
Potassium sparing diuretic
*Hyperkalaemia, gynaecomastia
X Hyperkalaemia, addison’s
! K+ increasing drugs, pregnancy
Beta adrenoceptor blockers
Labetalol
bisoprolol
metoprolol
Decrease sympathetic tone by blocking NAd and reducing myocardial contraction
decrease renin secretion Beta1
*Bronchospasm heart block reynauds lethargy impotence Mask tachycardia- sign of insulin induced hypoglycaemia
X Asthma, COPD, haemodynamic instability, hepatic failure
! non-dihydropyridines CCBs,
Alpha adrenoceptor blockers
Doxazosin
Selective antagonism of Alpha-1
reduce peripheral vasculature resistance
benign prostatic hyperplasia -Tamsulosin
*Postural hypotension dizziness syncope headache fatigue
X postural hypotension
! in patients affected by dihydropyridine CCB -oedema
Loop diuretic
furosemide
bumetanide
inhibit N/K/2Cl co-transporter in ascending limb
decrease N K and Cl into epithelium - H2O follows
Direct dilation if capacitance veins- reduces preload
for acute pulmonary oedema, fluid overload in HF, adjunct in nephrotic syndrome
*Dehydration Hypotension Hypokalaemia hyperuricaemia arrhythmia tinnitus cholesterol and triglyceride
X Hypokalaemia, hyponatraemia, gout, hepatic encephalopathy
! aminoglycosides, digoxin, lithium
Diuretic- potassium sparing
amiloride
Block ENaC
decrease Na reabsorption in DCT and reduce K secretion
*Hyperkalaemia
potential arrhythmia
X Addisons, potassium suppliments
! Other K+ sparing drugs, ACEi, ARBs
Statin
Simvastatin
Atorvastatin
Simvastatin is a prodrug t1/2 = 2h
Atorvastatin first pass- active derivatives t1/2 = 24h
competative inhibition of HMG-CoA reductase - upregulation of Hepatic LDL receptors - increase clearance of LDL
improved endothelium function
stabilisation of plaque
improved haemostasis
*GI disruption nausea headache diffuse muscle pain rare- rhabdomyolysis - OAT differences and skeletal muscle ATP production increased liver enzymes
X renal or hepatic impairment
! CYP 3A4 important - amiodarone, diltiazem, macrolides
amlodipine
Fibric acid derivatives (fibrates)
fenofibrate
activation of nuclear transcription factor - PPA&
PPAR& regulate expression of genes that control lipoprotein metabolism- increase production of lipoprotein lipase
^triglyceride removal from lipoprotein in plasma
^fatty acid uptake in liver
^HDL
^LDL affinity to receptor
*Gall stones,
GI upset
myositis
X photosensitivity, gall bladder disease
! Warfarin - increase coag
Cholesterol absorbtion inhibitors
ezetimibe
Inhibit NPC1L1 transporter at brush border in small intestines
reduces absorption 50%
hepatic LDL receptor expression increases
prodrug- hepatic metabolism- enterohepatic circulation- limits systemic exposure
secreted by bile
Adjunct to statin
*Abdo pain
GI upset
angioedema
X hepatic failure
! mindful with static- rhabdo
ciclosporin
PCSK9 inhibitors
Alirocumab
stops LDL being recycled
Bisphosphonates
Alendronic acid
reduce bone turnover
controls osteoclast activity
*oesophagitis
Hypocalcaemia
biguanides
metformin
decrease hepatic glucose production by inhibiting gluconeogenesis
supress appetite
*GI upset- nausea, vomiting, diarrhoea
X excreted unchanged by kidneys - stop if GFR <30mL/min
alcohol intoxication
! ACEi, diuretics, NSIADs - drugs that may impair renal function
loop and thiazide diuretics - ^glucose can reduce metformin action
sulfonylureas
gliclazide
Stimulate beta cell pancreatic insulin secretion
blocking ATP-dependent K+ channels
need residual pancreatic function
*mild GI upset, hypoglycaemia (works at low [glucose])
X hepatic and renal disease, those at risk of hypo
! other hypoglycaemics, loops and thiazides ^glucose can reduce its action
thiazolidinediones (glitazones)
pioglitazone
rosiglitazone
insulin sensitisation in muscle and adipose, decrease hepatic glucose output by activation of PPAR-gamma -> gene transcription
t1/2 not related to duration of action 6-8 weeks for benefit
weight gain
*GI upset
fluid retension
fracture rist
bladder cancer
X heart failure - fluid retension
! other hypoglycaemics
SGLT-2 inhibitors (gliflozins)
dapagliflozin
canagliflozin
decrease glucose absorption from tubular filtrate
increase urinary glucose excretion
competitive reversible inhibition of SGLT-2 in pct
Modest weight loss, hypoglycaemic risk low
TIIDM as add on therapy
*UTI and genital infection
thirst
polyuria
X hypovolaemia - possible hypotension
! antihypertensive and other hypoglycaemic agents
DPP-4 inhibitors
Dipeptidyl peptidase-4 inhibitors (gliptins)
sitagliptin
saxagliptin
prevent incretin degradation- ^plasma secretin conc
glucose dependent so postprandial action
do not stimulate insulin secretion at normal blood glucose- lower hypo risk
suppress appetite
*GI upset
spall pancreatitis risk
X pregnancy, history of pancreatitis
! other hypoglycaemics, drugs ^ glucose can oppose gliptins- thiazide and loops
Glucagon-like peptide-1 (GLP-1) receptor antagonists (incretin mimetics)
exentide
liraglutide
increase glucose dependant synthesis of insulin from beta cells
activate GLP-1 receptor- resistant to degredation by DPP-4
subcut
promote satiety
*GI upset, decreased appetite with weight loss
X renal impairment
! other hypoglycaemic agents
Class 1B agents
Lidocaine
mexiletine
lido- IV mex- orally
fast binding offset kinetics
no change in phase 0 in normal tissue (tonic block)
ADP slightly decreased (normal tissue)
increase threshold (Na+)
decrease phase 0 conduction in fast beating or ischaemic tissue
effect on ECG- normal in normal, ^QRS in abnormal
uses- acute: ventricular tachycardia
not used in atrial arrhythmias or AV junction arrhythmias
*CNS effects: dizziness, drowsiness
abdominal upset
Class 1C
Flecainide (propafenone)
very slow binding offset kinetics (>10s)
substantially decreased phase 0 (Na+) in normal
decreased automaticity (increase threshold)
increased APD (K+) and increased refactory period, esp in repidly depolarising atrial tissue
ECG: ^PR ^QRS ^QT
uses: wide spectrum
used for supraventricular arrhythmias (fibrillation or flutter)
premature ventricular contactions
wolff-parkinson-white syndrome
*pro-arrhythmia and sudden death especially with chronic use and in structural heart disease
flecanide flutter
CNS and GI effects
Class II propranolol bisoprolol metoprolol esmolol
^APD anf refactory period in AV node to slow AV conduction velocity
decrease phase 4 depolarisation (catecholamine dependent)
ECG: ^PR lower HR
uses: treating sinus and catecholamine dependent tachycardia
converting re-entrant arrhythmias at AV node
protecting the ventricles from high atrial rates
*bronchospasm
hypotension
X partial AV block or acute heart failure (are used in stable heart failure)
Class III
amiodarone
sotalol
Amiodarone: increase refractory period and ^APD (K+) decrease phase 0 and conduction (Na+) increase threshold decrease phase 4 (beta block and Ca2+ block) decrease speed of AV conduction
ECG: ^PR ^QRS ^QT decrease HR
Uses: very wide spectrum: effective for most arrhythmias
*Pulmonary fibrosis hepatic injury increase LDL thyroid disease photosensitivty optic neuritis (transient blindness)
! may need to reduce dose of digoxin and monitor warfarin more closely
Sotalol:
^APD and refractory period in atrial and ventricular tissue
slow phase 4 (beta blocker)
slow AV conduction
ECG: ^QT lower HR
uses: wide spectrum: supraventricular and ventricular tachycardia
*Proarrhythmia
fatigue
insomnia
Class IV
verapamil
Diltiazem
slow conduction through AV (Ca2+)
increase refractory period in AV node
increase slope of phase 4 in SA to slow HR
ECG: ^PR increase/decrease HR depending on BP and baroreflex
uses: control ventricles during supraventricular tachycardia
convert supraventricular tachycardia (re-entry around AV)
*GI (constipation)
caution when partial AV block is present - can get asystole if Beta blocker is on board
caution with hypotension, decreased cardiac output or sick sinus- slow sinus node
Class V
adenosine
rapid iv bolus
natural nucleoside binding to A1 and blocks adenylyl cyclase - reducing cAMP which activates K+ currents in AV and SA causing hyperpolarisation- stopping HR
leads to decreased Ca currents- increase refractory period in AV node
slows AV conduction
uses: convert re-entrant supraventricular arrhythmias
diagnosis of coronary artery disease (scans)
Class V
ivabradine
Blocks If (funny currents) highly expressed in SA
slows SA node but doesn’t effect BP
uses: reduce inappropriate sinus tachycardia, reduce HR in heart failure and angina (avoiding BP drops)
*flashing lights
teratogenicity not known
Class V
digoxin (cardiac glycosides)
enhances vagal activity (increases k+ currents, decreases Ca currents ^refractory period
slows AV conduction and slows HR
uses: treatment to reduse ventricular rates in atrial fib and flutter
Class V
atropine
selective muscarinic antagonist
block vagal activity to speed AV conduction and increase HR
Uses: treat vagal bradycardia
Cyclo-oxygenase inhibitor
aspirin
potent platelet aggregating agent thromboxane A2 (TXA2) formed from arachidonic acid by COX-1
aspirin inhibits COX-1 mediated production of TXA2 and reduces platelet aggregation- irreversible
higher doses inhibit endothelial prostacyclin (PGl2)
absorbed by passive diffusion- hepatic hydrolysis to salicylic acid
*GI irritation, GI bleeding, haemorrhage (stroke), hypersensitivity
X reye’s syndrome <16, hypersensitivity, 3rd trimester -closure of ductus arteriosus
! other antiplatelet and anticoagulants (additive/synergistic action)
ADP receptor antagonists
Clopidogrel
prasugrel
ticagrelor
inhibit binding of ADP and P2Y12 receptor – inhibit activation of GPIIb/IIIa receptors -independent of COX
clopidogrel (slower onset) and prasugrel are irreversible - prodrugs with hepatic active metabolites
*Bleeding
GI upset - dyspepsia and diarrhoea
rarely thrombocytopenia
X caution in high bleed risk patients with renal and hepatic impairment
! clopidogrel requires CYPs for activation
CYP inhibitors - omeprazole, ciprofloxacin, some SSRIs
need to concider use of other PPIs with clopidigrel
ticagrelor can interact with CYP inhibitors and inducers
caution when prescribed with other antiplatelet or anticoagulant
phosphodiesterase inhibitors
dipyridamole
inhibit cellular reuptake of adenosine = increased adenosine = inhibit platelet aggregation via adenosine A2 receptors
also acts as phosphodiesterase inhibitor preventing cAMP deg = inhibit expression of GPIIB/IIIa
*V+
dizziness
! antiplatelet and anticoags, adenosine
Glycoprotein IIb/IIIa inhibitor
abciximab
blocks binding of fibrinogen and vWF
target final common pathway - more complete platelet aggregation
*Bleeding - dose adjust for weight
! caution with other antiplatelet and anticoags
fibrinolytic
alteplase
streptokinase
convert plasminogen to plasmin
*Bleeding
! antiplatelets and anticoags
Azathioprine
Immunosuppressant
anti-metabolite DNA and RNA synthesis
*bone marrow suppression
malignancy risk
risk of infection
hepatitis
NSAIDs
inhibition of COX
decrease prostaglandin, prostacyclin and thromboxane synthesis
compete with arachidonic acid for hydrophobic site of COX enzymes
Analgesic:
Decrease PGE2 synthesis in dorsal horn - decrease neurotransmitter release - decrease excitability of neurones in pain relay pathway
Anti-inflammatory:
decrease in COX activity = less prostaglandin mediated increase in vasodilation so vasoconstriction and less oedema
Antipyretic:
inhibition of hypothalamic COX-2 where cytokine induced prostaglandin synthesis is elevated results in a reduction in temperature
*Dyspepsia nausea peptic ulcer -less mucus and bicarb ^acid, less blood flow bleeding perforation exacerbation of IBD Renal impairment hypernatremia
X elderly, prolonged use, smoking, alcohol, peptic ulcer Hx, h. pylori, CKD, heart failure
! Aspirin, glucocorticoid steroid, anticoag (PPI considered) ACEi, ARBs, diuretics
selective COX-2 inhibitors
celecoxib
etoricoxib
inhibits COX-2 more than COX-1
less GI ADR
does not share antiplatelet action but inhibits PGl2 - potentially leading to unopposed aggregatory effects
X increased risk of MI
paracetamol
COX-2 selective inhibition in CNS (spinal cord)
NAPQI
highly reactive metabolite- some analgesic effect suggested
harmless at therapeutic doses- conjugation with glutathione
-hepatic glutathione is limited
NAPQI highly neucleophilic - oxidising key metabolic enzymes - causing cell death- neurosis and apoptosis
N-Acetylcystine
glutathione thiol replacement - gets in hepatocyte
ICS
beclometasone
budesonide
fluticasone
activate cytoplasmic receptors, activated receptor then passes in to nucleus to modify transcription
reduces mucosal inflammation, widens airways, reduces mucus
reduces symptoms, exacerbations and prevents death
*can cause a local immunosuppressive action - candidiasis, hoarse voice
X Pneumonia risk in COPD at high doses
! Few if taken correctly
SABA
LABA
relaxes smooth muscle
prevention of bronchoconstriction prior to exercise
*Adrenergic- fight or flight effects Tachycardia palpitations anxiety and tremor ^glycogenolysis (liver) ^renin (kidney) SVT
X LABA should only be prescribed along ICS, CVD
! beta blockers may reduse effects of B2 agonists
LTRA
leukotriene receptor antagonist
montelukast
Block CysLT1 at CYSLTR1 that are released by mast cells/eosinophils
*headache
GI upset
dry mouth
hyperactivity
X used as add on in specific circumstances
! nothing major
LAMA
long acting muscarinic antagonist
tiotropium
block vagally mediated contraction of airway smooth muscle
*Infrequent- anticholinergic effects- dry mouth, urinary retension, dry eyes
X generally ok
adenosine receptor antagonist
theophylline
decrease bronchoconstriction
X narrow theraputic index - arrhythmia
! CYP450 inhibitors - increase conc
opioids
opioid receptor agonist
Morphine:
metabolism = morphine + glucuronic acid = M6G+M3G
*resp depression emesis decreased GI motility ^sphincter tone cardiovascular miosis histamine release -asthma caution
Fentanyl:
metabolism = CYP3A4
less histamine release
*resp depression
constipation
vomiting
Codine:
codine -> morphine via CYP2D6
CYP2D6 inhibited by fluoxetine
mild analgesia, cough depressant
*constipation
resp depression - worse in children
alginates and antacids
gaviscon
buffering in stomach
increase stomach content viscosity and reduce reflux
*Magnesium salts can cause diarrhoea and aluminium salts cause constipation
X Na and K containing preparations caution in renal failure
hyperglycaemia in DM
! can reduce absorbtion of many drugs - separate doses
increases aspirin excretion
PPI
Lansoprazole
Omeprazole
irreversibly inhibit H/K ATPase in gastric parietal cells
final stage in pathway- very significant reduction in acid secretion
*GI disturbance - abdo pain, constipation diarrhoea
Headache, dizziness
Drowsiness/confusion
X mask symptoms of gastro-oesophageal cancer
osteoporosis
! omeprazole CYP inhibitor - reduced clopidogrel action
PPIs can increase effects of warfarin and phenytoin - monitor
H2 receptor antagonists
ranitidine
inhibition of H2 receptors
only partial reduction because of other pathways
- generally ok, diarrhoea, headache
X mask symptoms of gastro-oesophageal cancer, renal impairment
! few
ranitidine - possible carcinogen
Aminosalicylates
Mesalazine
used for ulcerative colitis
release of 5-aminosalsylic acid - reduce inflamation
*GI disturbance - nausia, dyspepsia
leukopenia
X aspirin sensitivity
! enteric coated tablets may break down quicker in presence of PPI
