Pharmacology Flashcards
1
Q
5-Lipoxygenase
A
Converts Arachidonic Acid to Leukotrienes
2
Q
ACE Inhibitors
A
Angiotensin Converting Enzyme Inhibitors Block angiotensin I -> angiotensin II 'prils' Reduces blood volume and vascular tension (affects of Angiotensin II) Inhibits breakdown of Bradykinin
Contraindicated in pregnancy (teratogenic)
3
Q
Acetylcholine
- effects
- production
A
Neurotransmitter (ANS - CNS & PNS)
Only neurotransmitter used in the motor division of the somatic nervous system. Acetylcholine is also the principal neurotransmitter in all autonomic ganglia.
Has inhibitory effect in cardiac tissue (lower HR)
Excitatory neurotransmitter at neuromuscular junctions in skeletal muscle. Causes smooth muscle contraction at high concentrations
Choline + AcetylCoA = Acetylcholine + CoA
4
Q
Adrenaline, noradrenaline
- receptor
- production
(epinephrine, norepinephrine)
A
α and β-adrenoceptor agonist
Catecholamines
NA Synthesis
Tyrosine –(Tyrisoine Hydroxylase)–> L-DOPA –(DOPA decarboxylase)–> Dopamine –(Dopamine beta-hydroxylase)–> Noradrenaline
Adrenaline Synthesis
(as before) Noradrenaline –(Phenylethanolamine-N-methyl transferase)–> Adrenaline
Broken down by MAO (mono-amine oxidase)
5
Q
Alteplase
A
Fibrinolytic, activates plasminogen (to plasmin)
Clot Selective, Very Expensive
Short Half Life (IV infusion)
6
Q
Aminoglycosides
A
MECHANISM:
Bind to ribosome and distort reading frame (bacteria makes abnormal proteins) - leads to faulty cell wall.
Total protein synthesis block
BACTERIA: GNRs E coli Klebsiella Pseudomonas
NAMES:
Gentamicin
Tobramicin
Streptomycin (TB)
SIDES:
Hearing Loss
Vertigo
Kidney Damage
7
Q
Amiodarone
A
K+ Channel Inhibitor
Prolong cardiac action potential
Amiodarone also blocks Na+, Ca+, and β-adrenoceptors
Adverse effects:
reversible photosensitisation, skin discolouration, and hypothyroidism
Causes pulmonary fibrosis with long term use
8
Q
Ampicillin
A
Beta-lactam
GPC, GPR, GNC, GNR
Broad spectrum - binds many penicillin binding proteins and very soluble
Pseudomonas auriginosa are intrinsically resistant because they have a chromosomally encoded beta-lactamase
9
Q
Amrinone
A
Phosphodiesterase 3 Inhibitor Increase cAMP Increase Protein Kinase A (PKA) activity Increase intracellular Ca2+ Increase contractility (also causes vasodilation - cGMP)
10
Q
Angiotensin Receptor Antagonists
A
‘sartans’
vasodilation reduced blood pressure Reduce aldosterone Reduce cardiac hypertrophy Reduce sympathetic activity Adverse effects: hyperkalaemia headache, dizziness
11
Q
Aspirin
A
Acetylation of COX (inhibitor)
- anti-inflammatory
- Aspirin Triggered Lipoxins - resolution of inflammation
- analgesic
- anti-pyretic
- anti-coagulant (low dose 80mg)
- contraindicated in gout (competes with uric acid in kidney for excretion)
12
Q
Astemizole
A
H1 Receptor Antagonist (Competitive / Reversible)
Non sedative
Lack anti-muscarinic activity and GIT effects
13
Q
Atenolol
A
β1adrenoceptor antagonist (decrease HR & Contractility)
14
Q
Atropine
A
Anti-muscarinic (competitive antagonist at parasympathetic AChR)
Reduce secretions (e.g. Salivation)
Bronchodilator (in anaesthesia)
Treatment of bradycardia (block M2, parasympathetic)
Increase HR
Pupil dilation
AChE-inhibitor poisoning
15
Q
b-lactams
A
Inhibit bacterial cell wall synthesis
Include penicillins
16
Q
Botulinum Toxin
A
Prevents SNARE proteins from binding thereby preventing synaptic vesicle from releasing neurotransmitters
17
Q
Bradykinin
A
Autacoid
Prekallikrein -(hageman/Factor XII)-> kallikrein -> HMWK -> bradykinin
Degraded by ACE
Stimulate Release of PGI2 and NO (Vasodilation)
Stimulate sensory nerve endings (Pain)
Contract uterus, airways, gut (smooth muscle)
Epithelial secretion in airways, gut
18
Q
Ca2+ Channel Blocker
A
Cardioselective blockers (Verapamil) most effective at SA and AV nodes, reduce rate and conduction
Adverse effects:
Facial flushing, peripheral oedema, dizziness, bradycardia, headache, nausea
Verapamil
Diltiazem (also vasodilator)
Nifedipine
19
Q
Captopril, Enalapril, Perindopril, Ramipril
A
ACE Inhibitors (block angI -> angII) Reduce vascular tone (vasodilation) Reduce Aldosterone production Reduce Cardiac Hypertrophy Prevent Bradykinin breakdown Adverse Effects: First-dose hypotension Dry cough loss of taste hyperkalaemia acute renal failure itching, rash, angio-oedema foetal malformations
20
Q
Carbenicillin
A
GNR (Pseudomonas Aeruginosa)
21
Q
Cetirizine
A
H1 Receptor Antagonist (Competitive / Reversible)
Reduced risk of unwanted cardiac effects
22
Q
Chlopheniramine
A
H1 Receptor Antagonist (Competitive / Reversible)
Sedative
23
Q
Cholestyramine, colestipol
A
Bind bile acids (cholesterol metabolites) preventing gut absorbtion
Upregulation of hepatic LDL receptors (to synthesize bile acids)
Removal of LDL from plasma and increased cholesterol metabolism
ADVERSE EFFECTS:
abdominal discomfort, bloating, constipation, flatulence
rare: increased triglycerides, fecal impactions, decreased fat soluble vitamin absorbtion, fatty stool (steatthorea)
Decreased drug absorbtion (thiazides, aspirin, glucosides) - give drugs before resins
24
Q
Cisplatin
A
Cytotoxic anticancer agent (prostate tumors) Causes nephrotoxicity (blood & protein in urea, kidney damage)
25
Clavulanic Acid
Suicide inhibitor of β-lactamase
Doesn’t inhibit chromosomally encoded resistances
combine with amoxycillin (β-lactam)
26
Clopidogrel
ADP receptor antagonist
Inhibits platelet activation and adhesion
Oral prodrug
27
Cocaine
Block reuptake of Noradrenaline from synapse
(similar for dopamine and serotonin)
Produce tachycardic effect and heightened Blood Pressure, dysrhythmia
Also blocks Na+ channels - precursor for local anaesthetic drugs
28
COX
Cyclooxygenase
Catalyses Arachidonic Acid -> PGE2, PGD2, PGF2
COX1 - constitutive, COX2 - inducible (IL-1)
COX2 expressed in vessel wall by steady laminar shear stress
29
Digoxin
Glycoside
Decrease HR (increase vagal activity)
Increase contractility
- Inhibit Na+/K+-ATPase, increasing intracellular Ca2+
- Decrease Ca2+ in sarcoplasmic reticulum
Affects Gut, CNS, Cardiac
Forms complex with Aromatic hydrocarbon receptor nuclear translocator which increases P450 gene expresion
30
Dobutamine
β1 adrenoceptor agonist (increase HR & Contractility)
31
Donepezil
Anticholinesterase (acetylcholinesterase inhibitor)
Prevents breakdown of ACh
Enters CNS well
Treatment of Alzheimers
32
EC50
concentration of a compound where 50% of its maximal effect is observed
33
ED50
effective dose, for 50% of people receiving the drug
34
Edrophonium
Anticholinesterase
Short duration
Diagnosis of myasthenia gravis
35
Endothelin
Vasoconstrictor
| produced by vascular endothelium
36
Ezetimbe
Inhibits cholesterol absorbtion in intestine by binding to sterol transporter
Does not affect absorbtion of bile acids or fat soluble vitamins
lowers LDL
ADVERSE EFFECTS:
diarrhoea, headache, tiredness
allergic reaction, severe joint or stomach pain
37
Flecainide
Class 1c Na+ Channel Blocker
Marked Na block
Same repolarisation
No effect on ERP
38
Flucloxicillin
GPC (Staphylococcus)
| beta-lactam with narrow-spectrum
39
Furosemide / Frusemide
```
Loop Diuretic (loop of henle)
inhibit Na+/K+/2Cl- carrier into cells
Well absorbed (<1hr)
Duration (3-6 hours)
Adverse effects:
hypokalaemia
metabolic alkalosis
hypovolaemia and hypotension
```
40
Gemfibrozil, fenofibrate
Fibrates - lower lipid levels
Agonist at nuclear receptor (regulate gene expression)
peroxisome proliferator activated receptor alpha agonist
increased synthesis of liproprotein lipase (LPL)
increased lipolysis of lipoprotein TG
reduction in plasma TGs
increase in HDL
variable effect on LFL
ADVERSE EFFECTS:
elevation of serum aminotransferase
nausea, dry mouth, headache, rash
rare: arrhythmias, gallstones, photosensitivity, impotence, depression
41
Gentamicin
Aminoglycoside
High toxicity (renal elimination damages kidney and impares excretion)
42
Glycopeptides
MECHANISM:
Target bacterial cell wall (inhibit peptidoglycan synthesis)
BACTERIA:
GPs (including MRSA)
C difficle
NAMES:
Vancomycin
43
Glycosides
Gut - anorexia, nausea, diarrhoea
CNS - drowsiness, confusion, psychosis
Cardiac - ventricular dysrhythmias
see digoxin
44
Heparin
Anticoagulant
Enhance activity of anti-thrombin III which inhibits IIa (Thrombin) IXa, Xa, XIa, XIIa
Given via IV (large & negative charged molecule)
Measured by APTT (activated partial thromboplastin time) - time it takes for blood to clot
45
Hexamethonium
Ganglion Blocker
| Nicotinic AChR antagonist
46
Histamine
```
H1:
Vasodilation,
Vascular Permeability
Bronchoconstriction
Smooth muscle contraction
+
Pain & itch (sensory nerve activation)
Mucous secretion
CNS - increased wakefulness
```
H2:
Gastric acid secretion
Positive inotropic and chronotropic effects
47
Hydrochorothiazide
Thiazide Diuretic
inhibity Na+/Cl- cotransporter in distal convoluted tubule
lower blood volume and reduce BP
Adverse effects:
K+ loss, gout, hyperglycaemia, allergic reaction
48
Ipratropium Bromide
```
Treatment of COPD
Anti-muscarinic (non selective)
blocks muscarinic (M3) AChR in smooth muscle of bronchi
Tiotropium Bromide (LAMA), M3 selective.
```
49
Isoprenaline
β1& β2 adrenoceptor agonist
50
K+ Channel Block
Delay phase 3 of ventricular action potential (K+ efflux)
Decrease incidence of re-entry
Increase risk of triggered events
51
Lignocaine
Class 1b Na+ Channel Blocker
Mild Na block
Decrease ERP
```
Local Anaesthetic (aminoamide) - prevent action potention transmission
Long acting, hepatic metabolism
```
52
Loop Diuretics
```
Act on thick ascending limb of loop of henle
inhibit Na+/K+/2Cl- carrier into cells
Well absorbed (<1hr)
Duration (3-6 hours)
Adverse effects:
hypokalaemia
metabolic alkalosis
hypovolaemia and hypotension
```
53
Loratidine
H1 Receptor Antagonist (Competitive / Reversible)
| Reduced risk of unwanted cardiac effects
54
Losartan, Candesartan
```
Angiotensin Receptor (AT1/AT2) Antagonist
Reduce vasoconstriction
Reduce aldosterone
Reduce cardiac hypertrophy
Reduce sympathetic activity
Adverse effects:
hyperkalaemia
headache, dizziness
```
55
LTB4
Leukotriene B4
| Promotes Inflammation by attracting leukocytes
56
LTC4, LTD4, LTE4
```
Leukotreines
Bronchoconstrictors
Vasoactive
Vessel permeability
Increased mucous production
Asthma (w/ aspirin)
Inhibited by Montelukast
```
57
MAOI
Monoamine Oxidase Inhibitor
| prevent breakdown of Noradrenaline, increasing rate of secretion and synaptic concentration
58
Methicillin
GPC (Staphylococcus)
59
Metronidazole
Avtivated by strict anaerobe reducing enzymes (used to keep environment free of oxygen)
Also good for trichnomoniasis, amoebiasis, and giardiasis
60
Muscarinic AChR
```
G-Protein Coupled Receptor
Autonomic NS
Salavation, Lactimation, Urination, Defecation
Sweating
Decrease HR
Bronchoconstriction
Vasodilation
```
61
Na+ Channel Block
Reduce phase 0 slope and peak of ventricular action potential (depolarization involving Na+ influx)
Quinidine 1a
Lignocaine 1b
Flecainide 1c
62
Neostigmine, Pyridostigmine
Anticholinesterase
Reverse effect of non-depolarising neuromuscular blockers
Treatment of myasthenia gravis (LMNL)
63
Niacin / Nicotinic Acid
For treatment of hypercholesterolaemia (mechanism unclear)
decrease VLDL secretion
reduction in plasma LDL and TG
increase in HDL
decrease lipoprotein(a) - formed from LDL in plaques and inhibits thrombolysis
```
ADVERSE EFFECTS:
Vasodilation, flushing, hypotension
Nausea, vomiting
Tolerance
Rare: itching, glucose intolerance, uric acid retention, hepatic imparement
```
64
Nicotinic AChR
Ligand Gated Ion Channel
Somatic NS / Autonomic NS
Skeletal (Somatic) muscle contraction
65
Nitrates
```
Venodilators (primarily)
Some vasodilation
Treatment of Angina
1st pass metabolism
increased tolerance (and sensitivity to constrictors)
Reduce preload & cardiac work
```
release NO -> stimulates guanylate cyclase in smooth muscle -> GTP converted to cGMP-> myosin LC-PO4 dephosphorylated to myosin LC -> vascular relaxation
```
ADVERSE EFFECTS:
relaxation of gut, airway smooth msucle
postural hypotension (venous pooling)
headache, flushing
reflex tachycardia (usually given in combination with beta-blocker to minimize)
```
66
Nitric Oxide (NO)
Vasodilator
Inhibit platelet adhesion and aggregation
Also known as Endothelium Derived Relaxant Factor
Increased intracellular Ca2+ catalyses NOS inactive to NOS active which catalyses arginine to NO + citrulline
NO catalyses pathway causing cGMP production (relaxation). cGMP is degraded to GMP (can be blocked by Viagra)
67
NSAID
Inhibit COX
- anti-inflammatory
- analgesic
- anti-pyretic (reduce fever)
- anti-coagulant
SIDES:
- increased bleeding time (decrease TXA2)
- GI (reduced mucous, increased acid, reduced blood flow and angiogenesis)
- reduced renal blood flow (decreased PGI dilation)
- triple whammy
- bronchoconstriction (overproduction of leukotrienes)
68
Osmotic Diuretics
```
pharmacologically inert (e.g. mannitol sugar molecule)
reduce passive water reabsorbtion
use in raised intercranial/interocular pressure
prevent acute renal failure
```
69
Penicillin G
GPC, GPR, GNC
| Bacteriostatic (bacteria detect cell wall defect and break down their own wall)
70
Penicillin V
GPC, GPR, GNC
| less effective than penicillin G against Gram negatives
71
PGD2
Bronchoconstrictor
| Does not circulate
72
PGE2
```
Vasodilator (decrease BP)
Angiogenic (healing)
Pyrogenic (fever)
Hyperalgesic (pain)
Increase mucous secretion
Decrease gastric acid secretion
Does not circulate
Induction of labour & abortant
```
73
PGF2
Bronchoconstrictor
| Does not circulate
74
PGI2
```
Prostacyclin
Vasodilation,
Inhibits platelet aggregation/activation
Anticoagulant
Secreted by vascular endothelium
```
75
Phenylephrine
α1 adrenoceptor agonist (vasoconstrictor)
| useful as nasal decongestant
76
Phospholipase A2
Releases Arachidonic Acid from Cell Membrane
77
Pilocarpine
Reduce interocular pressure (glaucoma)
| Autonomic NS Muscarinic AChR agonist
78
Polyenes
| - amphotericin B
Antimicrobial targets fungi
Attacks ergosterol in cytoplasmic membrane (very toxic - also attack cholesterol)
Cause K+ and Na+ leakage -> cell death
allylamines, triazoles (fluconazole), morpholines affect synthesis of ergosterol
79
Polymyxins
Attack cytoplasmic membrane (best antifungals we have)
80
Potassium-Sparing Diuretics
```
Act on collecting tubule and ducts
Block aldosterone (compete for Aldosterone Receptor)
- blocks Na+ channel activity and Na+/K+ channel synthesis
```
81
Potency
How small a dose you can get away with and be effective
Low potency is only a disadvantage if dose is large and awkward to administer
More potent =/= clinically superior
82
Promethazine
H1 Receptor Antagonist (Competitive / Reversible)
| Sedative
83
Propanolol
β1& β2 adrenoceptor antagonist
Reduce Cardiac Output (Rate/Contractility)
Reduce Renin Release (Blood Volume/TPR)
Adverse effects:
Cold extremities (alpha1-adrenoceptor constriction)
Fatigue
Dreams / Insomnia
Bronchoconstriction (beta2-adrenoceptor blockade in airway smooth muscle)
84
```
Propanolol
Timolol
Atenolol
Metoprolol
Pindolol
```
β-adrenoceptor antagonists
Reduce Cardiac Output (Rate/Contractility)
Reduce Renin Release (Blood Volume/TPR)
Propanolol/Timolol = b1 & b2
Atenolol/ metoprolol = b1
Pindolol = b1/b2 partial agonist
Adverse effects:
Cold extremities (alpha1-adrenoceptor constriction)
Fatigue
Dreams / Insomnia
Bronchoconstriction (beta2-adrenoceptor blockade in airway smooth muscle)
85
Quinidine
Class 1a Na+ Channel Blocker
Moderate Na block
Prolong repolarisation
Increase ERP
86
Salbutamol
β2 adrenoceptor agonist (Bronchial smooth muscle relaxant)
Short acting
Possible tolerance (use partial agonist to avoid tolerance)
87
Spironolactone
Aldosterone Receptor Antagonist
Inhibit Aldosterone action on cortical and distal tubules
K+ sparing
Reduced activation of Na+ channels
Reduced stimulation of Na+ pump synthesis
88
Statins
Competitive inhibitor of HMG-CoA reductase (cholesterol pathway).
Deplete Q10 (ubiquinone / coenzyme Q)
Concern that statins displose to Type II diabetes and dementia
Rosuvastatin (Crestor)
Lovastatin (Mevacor)
Pravastatin (Pravachol)
Simvastatin (Zocor)
Compactin
aviod grapefruit juice
cytochrome pathway (increase levels by antibiotics / antifungals, decrease by barbituates, phenytoin)
ADVERSE EFFECTS:
myopathy (treat with Q10)
rhabdomyolysis
renal failure, hepatitis, liver failure
89
Streptokinase
Activates plasminogen causing fibrinolysis
Antigenic (so single use only)
IV
90
Sympathomimetics
Displace Noradrenaline from vesicle and cause transport out into synampse by uptake-1 channel working in reverse
Ephidrine
Tyramine (found in foods - cheese,wine,choc)
Amphetamines (NA, 5-HT, DA release)
- increase mood, euphoria, alertness, locomotor, behaviour, confidence
- cause anxiety, tremor, confusion, tachycardia, BP
- suppress appetite
- dependence due to DA & withdrawal
91
Terfenadine
H1 Receptor Antagonist (Competitive / Reversible)
Non sedative
Lack anti-muscarinic activity and GIT effects
92
Tetracycline
| Doxycycline
```
MECHANISM:
Inhibit protein synthesis
Bind to 16S part of 30S ribosomal subunit
Bacterial resistance via:
- inactivation of tetracycline
- Efflux
- Ribosomal protection
```
93
Thiazide Diuretics
```
Act on distal convoluted tubule
Inhibit Na+/Cl- cotransporter
Orally active
Max effect (4-6hours)
Duration (8-12 hours)
Adverse Effects:
gout
(as for loop diuretics)
```
94
Tirofiban, Abciximab
Glycoprotein IIb/IIIa receptor antagonist
Inhibits platelet adhesion to fibrin
IV administration
95
Triamterene, Amiloride
Diuretic
Block luminal sodium channels in collecting tubules and ducts (inhibit Na reabsorbtion and K secretion)
Trimaterene: well absorbed, 2 hour onset, 12-16 hour duration
Amiloride: poorly absorbed, slow onset, duration 24 hours
96
Tubocurarine, Vecuronium
Pre-surgical muscle relaxant
| Nicotinic AChR antagonist
97
TXA2
Thromboxane A2
Produced by platelets
Increases platelet aggregation
vasoconstrictor
98
Vancomycin
Blocks enzymes that catalyse construction of peptidoglycan wall - binds D-ala, D-ala
Large molecule with lots of charged groups, not soluble in lipid, acts only on gram positive bacteria, can't penetrate cell walls
Glycopeptide antibiotic
Primarily used against resistant Gram positive bacteria (but not MRSA)
99
Verapamil
Ca2+ Channel Blocker (significant effect on cardiac and vascular muscle)
Slow conduction velocity and increase refractoriness
Cause facial flushing, peripheral oedema, dizziness, bradycardia, headache, nausea, AV block
100
Verapamil
Diltiazem
Felodipine
Nifedipine
Ca2+ Channel Blockers
Inhibit voltage gated L-type Ca2+ Channels (Ca2+ influx into heart)
Decrease HR, SV, CO, reduce demand, reduce supply
Primarily verapamil and diltiazem (some vascular effect)
ADVERSE: flushing, headache, oedema, bradycardia, AV block
Felodipine & Nifedipine have greater vasular effect than cardiac (can be used for hypertension)
Block Ca2+ influx into vessels
Arterial dilation, reduced afterload and demand
ADVERSE: hypotension, flushing, headache, oedema, reflex tachycardia
101
Vitamin K
Essential for formation of clotting factors II, VII, IX, and X
102
Volume of Distribution
```
Vd = X / C
X = amount in body
C = concentration in plasma
```
103
Warfarin
```
Inhibit reduction of Vitamin K thereby inhibiting production of clotting factors II, VII, IX, and X
Moody Drug (strongly bound to protein)
Rapid absorbtion
Orally Active
Competition for Cytochrome P450 pathway
PT & INR used for monitoring levels
```
Contraindicated in pregnancy (teratogenic)
104
β-adrenoceptor agonist
Noradrenaline / adrenaline (alpha and beta adrenoceptors)
Dobutamine (selective b1)
Amrinone (phosphodiesterase inhibitor)
105
β-adrenoceptor antagonist
Inhibit sympathetic influence on cardiac electrical activity
Decrease Rate and conduction (SA node)
Reduce renin release (decrease blood volume & TPR)
'olols'
Adverse effects: Bradycardia, reduced exercise capacity, hypotension, AV conduction block, bronchoconstriction, hypoglycaemia
106
Glyceryl Trinitrate (GTN)
```
Nitrate for use in angina
Smooth muscle relaxant & venodilator
1st pass metabolism
sublingual for acute attack
transdermal for prophylaxis
IV for emergency
unstable (light sensitive)
```
Reduces preload & cardiac work
107
Isosorbide Dinitrate
Nitrate for use in angina
Smooth muscle relaxant & venodilator
1st pass metabolism
active metabolite - canm be given orally
108
Ivabradine
Reduce HR
Inhibit inward Na+/K+ If current in SA
Decrease velocity of diastolic depolarization
Reduce Myocardial oxygen demand (and maxes supply)
ADVERSE EFFECTS:
brightness in visual field
conduction abnormalities
109
Efficacy
The capacity to produce an desired effect.
(Pharmacological) The strength of the receptor activation.
(Clinical) The strength of the beneficial effect.
Emax refers to the maximum response achievable from a drug
110
Angiotensin II
Increased sympathetic activity (vasoconstriction)
Acts on cardiovascular control centre to increase sympathetic output to heart
Na+, Cl- reabsorbtion
K+ excretion
H20 retention
Acts on adrenal cortex to increase aldosterone secretion (Na+ retention)
Acts on hypothalamus to increase ADH (vasopressin) secretion
Stimulates thirst
111
Icatibant
Bradykinin inhibitor (B2 receptor antagonist)
112
Erythropoietin
A glycoprotein hormone that controls erythropoiesis, or red blood cell production.
Produced by interstitial fibroblasts in the kidney in close association with peritubular capillary and tubular epithelial tubule
113
Glucocorticoids
regulate cytokines (IL-1, TNF, IL-5)
```
TRANSACTIVATION
GR dimerises,
binds GRE (promote anti inflammatory genes)
- annexin-1 (suppress phospholipase A2)
- serpin a3 (inhibit proteases)
```
TRANSREPRESSION
phosphorylates AP1 (activated protein 1)
bind NF-kB
Inhibits transcription of pro inflammatory genes
Used for:
Addison's disease, asthma, topical, hypersensitivity, rheumatoid arthritis
114
Omalizumab
Inhibit mast cell activation
Prevents IgE binding to alpha chain of FCeR1
Expensive
115
Roflumilast
Phosphodiesterase Inhibitor
Prevents breakdown of cAMP -> amp thereby causing smooth muscle relaxation
Used in the treatment of COPD
116
```
What do the following target?
Tetracyclines, aminoglycosides
polyene antibiotics
penicillin, cephalosporin, vancomycin
sulphonamides, trimethoprim
quinolones, rifampicin
```
Tetracyclines, aminoglycosides - RIBOSOMES
polyene antibiotics - MEMBRANE
penicillin, cephalosporin, vancomycin - CELL WALL
sulphonamides, trimethoprim
quinolones, rifampicin
117
Sulfanilamide/Sulfonamides
```
inhibits PABA -> folate (blocks dihydropteroate synthase)
resembles PABA (p-amino benzioic acid) in folic acid
folic acid is important in bacterial pathway for creating DNA
```
118
Trimethoprim
blocks dihyrofolate reductase enzyme
inhibits folate -> tetrahydrofolate (for bacterial DNA)
used for UTIs (cleared by kidney in active form)
119
Cotrimoxazole
Sulfamethoxazole (sulfanilamide) + trimethoprim
| Synergistic
120
Methotrexate
used for cancer (high dose), rheum arth (low dose)
inhibits purine synthesis
inhibit dihyrofolate reductase (low affinity for bacterial form)
inhibits WBC & RBC and causes GIT disorders
teratogenic, therefore risk of OD
121
Triple Whammy
Diuretic + ACE inhibitor (or AT1 antagonist) effective for hypertension
NSAID = acute renal failure because prostaglandin mediated vasodilation preserves renal blood flow.
122
Anakinra
```
IL-1 receptor antagonist
Rheumatoid Arthritis
Destructive Oesteoarthritis
Type II Diabetes
contraindicated for neutropenia
```
123
Cimetidine, Ranitidine
H2 receptor antagonists
Treatetment of peptic ulcer disease
Inhibit histamine action on parietal cell
Decrease gastric acid secretion
124
Omeprazole, Esomeprazole
Proton Pump Inhibitors (Irreversible)
Enterocyte luminal H+/K+ ATPase Inhibition
Decrease gastric acid secretion
125
```
Magnesium Hydroxide/carbonate/oxide/trisilicate
Sodium Bicarbonate
Aluminium Hydroxide
Calcium Carbonate
Gaviscon
```
Antacids
Neutralize gastric acid
Used in combination because of sides
Magnesium - induce diarrhoad
Sodium Bicarb - systemic alkolosis
Aluminium - constipation
Calcium - constipation & rebound acidity (gastrin release)
126
Sucralfate
Cytoprotective
| Coats stomach ulcer site and protects from acid
127
Hyoscine butylbromide
```
Muscarinic Receptor Antagonist
Reduces GI motility
Quarternary structure - not absorbed (BBB)
also known as Buscopan
Peptic ulcer treatment
```
128
Hyoscine hydrobromide
Muscarinic Receptor Antagonist
inhibit SLUD (salivation, lacrimation, urination, defecation)
Tertiary amine - absorbed (BBB), sedative
effective at reducing motion sickness
Sides: dry mouth, blurred vision, urinary retention, constipation
129
Mebeverine
Direct spasmolytic
| action unknown
130
Misoprostol
Prostaglandin E analogue
Increase mucous secretion, decrease gastric acid secretion
abortion (prostalandins increase uterus contraction/motility)
cytoprotective
131
Prometazine
Anti-Emetic
Histamine H1-receptor antagonist
Act on chemoreceptor trigger zone outside BBB to inhibit vomiting
effective at reducing motion sickness
known as Phernergan
132
Metoclopramide
| Prochlorperazine
Anti-Emetic
Dopamine D2-receptor antagonist
Act on chemoreceptor trigger zone outside BBB to inhibit vomiting
Metaclopramide - facilitates gastric emptying (pro-motility)
- helpful for migraine suffers (due to gastric stasis)
- used for treatment of gastroparesis
Potent D2 antagonist (Dopamine inhibits ACh in gut)
Weaker 5HT3 antagonist
Potent 5HT5 agonist - releases ACh -> increased motility
133
Dolasetron
Serotonin 5HT3 receptor antagonist
very few side effects, typically used in hospital
Act on vagal sensory afferents, reduce activity of messages to Chemoreceptor Trigger Zone
134
Aprepitant
Substance p antagonist
(Neurokinin1 Receptor Antagonist)
Substance p - pain inducing substance, can cause nausea and vomiting. NK1 receptors in Chemoreceptor Trigger Zone.
135
Dexamethasone
Glucocorticosteroid (20-30x more potent than cortisol)
Anti-inflammatory
Anti-emetic effects (Mechanism unknown)
Used for:
- Oncology, Obstetrics, High Altitude Sickness, Adrenal insufficiency and Addison's Disease
136
Docusate
Typically in combination with Senna
| Makes faeces softer and easier to pass
137
Magnesium Sulphate
Osmotic Laxative
| causes osmotic fluid retention & colonic distension -> increased motility
138
Bisacodyl
| Senna
Stimulant laxative
| Stimulates colonic myenteric nerve plexuses
139
Loperamide
```
Opioid (all opioids cause constipation including codeine)
Antidiarrhoeal
Does not cross BBB
Localised effects
Very potent at stopping diarrhoea
```
140
Simethicone
Treatment of flatulence
Stays in gut (not absorbed)
Changes surface tension of air bubble causing them to coalesce into large bubbles easily passed
141
Pharmacological Management of Alcohol
Disulfiram (antabuse) - inhibit aldehyde dehydrogenase
Naltrexone - opioid receptor antagonist - diminishes pleasure
Nalmefene - opioid receptor antagonist
Tiapride - D2 receptor antagonist - eases withdrawal symptoms
Acamprosate - GABA receptor agonist - eases withdrawal
142
Orlistat
Reduces fat absorption
Lipase inhibitor
prevents Tryglicerides from being broken into free fatty acids
SIDES: Explosive diarrhoea, faecal fat leakage, lowered vitamin absorption
143
Cyclosporin
Selectively takes out recently activated T Cells
Used for transplant immunosupression
Decreases IL-2 gene transcription (activation/proliferation of T Cells)
nephrotoxicity & susceptibility to viral infections
144
Dopamine
```
Catecholamine
Derived from Tyrosine,
precursor to Noradrenaline/Adrenaline
Actions in pleasure centre of brain (nucleus accumbens & vental tegmental) - reward/dependence
Cause prolactin secretion
Frontal cortex is dopamine rich
```
Parkinson's: depletion of dopamine in basal ganglia
Dopamine causes vomiting in systemic circulation
Broken down by MAO
see: Levodopa (L-DOPA)
145
Benzodiazepines (Diazepam/Valium)
Enhance inhibitory input
- enhanced GABA A receptor activity (act at allosteric site)
- Increases frequency of GABA A receptor Cl- channel opening (has ceiling effect)
- Increase POTENCY of GABA
Used For:
- Epilepsy, anxiety, sleep disorder, pre-surgery, alcohol withdrawal
Sides:
- Drowsiness, Confusion, Impaired Co-ordination, interaction with alcohol&antihistamines, withdrawal, dependence
Time:
(6-12): Oxazepam, Temazepam
(>24): Clonazepam, Diazepam
Zoplidem/Zoplicone: non-benzodiazepine's but similar action
146
Phenytoin <- most important
Ethosuximide
Felbemate
Reduce excitatory input
- Phenytoin - limit excitatory nerve activation
- good for epilepsy
- inhibits Na+ channels
- Na+ channel must be open to allow drug binding (i.e. enhanced during high frequency firing)
- Ethosuximide - inhibit T-type Ca2+ channels
- Felbemate - Inhibit NMDA receptor (on motor nerve)
147
Sedative & Anxiolytic Agents
SEDATION
- H1 receptor antagonists are sedative
ANXIETY:
- Serotonin
- Noradrenaline
- Neuropeptide Y (activation reduces anxiety)
- β-adrenoceptor (peripheral signs only)
COMBINED:
- GABA (Benzodiazepines, Barbiturates)
148
Barbiturates
```
CNS depressant (sedation->death)
Dangerous!
```
- enhanced GABA A receptor activity
- Prolong time of GABA A receptor Cl- channel opening (overdose)
- Increase EFFICACY of GABA
Low therapeutic Index
Addictive
149
Advantages of Allosteric Modulators
- Ceiling of effect of inhibitors (increased therapeutic window)
- Positive modulation of endogenous agonist (physiological regulation continues)
- Greater receptor subtype selectivity possible
150
Aldosterone
released from adrenal cortex by angiotensin II, [K+], and ACTH
increase Na+ reabsorption
increase K+ secretion
spironolactone blocks activity
151
Vasopressin (ADH)
osmoreceptors in hypothalamus detect high osmolarity
Vasopressin released from posterior pituitary
Aquaporins inserted into collecting duct epithelium
Increased water reabsorption
152
Levodopa
```
Dopamine Precursor (require dopaminergic neuron to be converted)
Peripheral conversion to dopamine: nausea, vomitting, hypotension, arrythmia
Reduces rigidity/tremors of parkinsons
Rapid absorption & short half life (1-2 hours)
Causes increased degeneration of dopaminergic neurons
```
Adverse Effects:
Hallucinations, abnormal movement, depression, anxiety
Interactions:
MAOI, B6, anticonvulsants, anaesthetics (inhaled)
153
MDMA
MethyleneDioxyMetAmphetamine
Releases DA & 5-HT
```
Stimulant & hallucinogenic
Dependence due to DA
Increase HR, BP
Chills & sweats
Degeneration of neurons (ROS) -> mood affects
```
154
LSD
Lysergic Acid Diet Hylamide
Hallucinations
Dependence & Tolerance
Cross tolerance w/o psychotomimetics
5-HT agonist
155
Caffeine
Delays onset of sleep
Postpone boredom, inattentiveness
Anxiety, tension, tremors
Adenosine antagonist, phosphodiesterase inhibitor (HR, BP & gastric acid secretion)
No dependence but 'weekend headache'
156
Ethanol
CNS depressant
Inhibit Ca2+ channel opening (stop neurotransmission)
Ehnace GABA
Inhibit glutamate
Tolerance & Dependance (withdrawal)
- anxiety, insomnia, delirium, hypotension, sweating
157
Cannabis / THC
Heightened sensory awareness and intensity
Relaxation
Dependence in heavy users
```
Cannabinoid receptors (GPCR)
- inhibit adenylate cyclase (similar to muscarinic receptors in heart) -> therefore inhibit inhibition
```
CB1 - CNS
* impaired memory & motor control
* catalepsy
* analgesia
* anti-emetic & increase appetite
CB2 - PNS receptors
* tachycardia, sympathetic ++
* vasodilation
* reduced interoccular pressure (glaucoma)
* bronchodilation
158
Antidepressants
- Tricyclic
- MAOI
- SSRI/SNRI
Tricyclic (imipramine, amitryptiline, doxepin):
- inhibit neuronal uptake of NA & 5HT
- poor selectivity, narrow therapeutic window & delayed clinical effects
- muscarinic, histamine, 5-HT, α-adrenoceptor antagonist
- sedation, hypotension, weight gain, confusion, mania, dysrhythmias
MAOI:
- increase 5-HT, NA (and DA)
- irreversible (phenelzine, tranylcypromine) - cheese reaction
- reversible (moclobemide) - MAO A selective
- hypotension, dizziness, nausea, insomnia
SSRI/SNRI (fluoxetine, paroxetine, sertraline, venlafaxine)
- selective for 5-HT
- few adrenergic, histaminergic, and cholinergic reaction
- adolescent -> suicidal tendencies
- nausea, insomnia, agitation, weight change, decreased libido
159
Pegvisomant
GH antagonist
PEGylated (long half-life, reasonable affinity)
Used in treatment of excessive GH
Could also use somatostatin (GHIH) or dopamine agonist to inhibit GH release from anterior pituitary
160
Octreotide
| Lanreotide
Somatostatin analogues (unnatural amino acids to avoid enzymatic cleavage)
Act as Growth Hormone Inhibiting Hormones (GHIH)
Longer half lives than somatostatin
+ Dopamine antagonists (bromocriptine or cabergoline) may increase effectiveness
161
PEGylation
* increase size of bioactive molecule -> reduce renal clearance
* Hydrophilicity improves solubility
* Decreased accessibility for proteolytic enzymes
* Occurs at lysines (important for molecules that use lysine @ binding site like GH)
162
Carbimazole
Inhibits thyroid peroxidase
Once daily dosing
- may lead to goiter, or hepatotoxicity
163
Propylthiouracil
Inhibits thyroid peroxidase AND conversion of T4 to T3
2-4 doses daily
- may lead to goiter, or hepatotoxicity
164
Exogenous Liothyronine (T3)
Thyroid hormone
More active than T4 and acts more rapidly
Less strongly bound to proteins
1day Half Life
Levels less stable -> TSH levels less easily interpreted
Inhibits cortisol (cortisol also inhibits T3)
165
Exogenous Thyroxine (T4)
```
Thyroid Hormone
99.96% bound to plasma proteins
Vd = 10Litres
7day Half life
slow onset of action may lead to poor compliance
```
166
Cyproterone Acetate
Inhibitor of androgen receptor
Blocks synthesis of mRNA for androgenic proteins
Treatment of Hirsutism, M2F, and castration
167
Beclomethasone
Nasal spray (Beconase)
Glucocorticoid
Treatment of allergies and recurrence of nasal polyps following surgical removal
168
Prednisolone
Glucocorticoid
Used for Asthma, Eczema, Nasal Congesion
Sides similar as for high cortisol
Progressively reduce dosage to avoid adrenal insufficiency
169
Leuprorelin
GnRH analogue
Used to induce chemical castration via inhibition (overstimulation) of FSH and LH release
Also has application in treating breast, ovarian, and prostate cancer
170
Tamoxifen
Selective oestrogen receptor modulator (SERM)
Breast - antagonist
Endometrium - agonist
Bone - agonist
Used in treatment of breast cancer (tamoxifen) and osteoporosis (raloxifene)
[fulvestrant is a complete oestrogen antagonist]
Adverse effects:
- endometrial hyperplasia, polyps, cancer
- thromboembolic events
- thrombocytopaenia
- occular toxicity
- menopausal symptoms
171
Letrozole
Aromatase inhibitor
Used in treatment of breast cancer
172
Dianabol
Anabolic Steroid
Increases production of actin and myosin (hypertrophy)
Reduces recovery time by blocking clortisol on muscle tissue (therefore preventing catabolism)
Decrease fat by increasing BMR
Sides:
liver damage, high BP, jaundice, renal failure, acne
Delusions, jealousy, paranoia, irritability
Reduced sperm count, shrinking testes, infertility, prostate cancer, baldness
Facial hair growth, deepened voice, oligomenorrhoea
Stunted growth, developmental problems
173
Ciclesonide
Third generation glucocorticoid
Reduced systemic effects after inhalation
* activation in lungs (not mouth/larynx)
* lipophillic (retained in tissues)
* low bioavailability (hepatic 1st pass metabolism)
* highly protein bound
174
Allopurinol
Xanthine Oxidase inhibitor
Prevents the formation of Uric Acid
Used in the treatment of Gout
175
Insulin
- long acting
- short acting
Isophane
Glargine
Detemir
Neutral
Glulisine
Lispro
Aspart
176
Sulphonylureas & Meglitinides
Used for Type II Diabetes (relative lack of insulin)
Inhibit pancreatic β-cell K+ channel
- > depolarisation and Ca2+ entry
- > insulin secretion
HL: 6-24 hours
Can cross placenta (contraindicated in pregnancy)
Excreted via kidney
SIDES: hypoglycaemia, weight gain
177
Biguanides (Metformin) & Thiazolidinediones
Used for Type II Diabetes (Insulin resistance)
Increase insulin-mediated peripheral glucose uptake
Reduce hepatic glucose production
Decrease carbohydrate absorption, LDL & TAG levels
Activates AMP Kinase (increases metabolism)
SIDES: GI disturbance, lactic acidosis, weight loss, contraindication w/ renal dysfunction
178
Alpha-glucosidase inhibitors
Block enzymes of digestion and absorption in small intestine
Not absorbed from GI
SIDES: flatulence, loose stool, abdo pain / discomfort, contraindicated w/ IBD or cirrhosis
179
Exenatide
```
Incretin for treatment of Type II Diabetes
GLP-1 agonist
increase glucose-mediated insulin
decrease glucagon
slow GI emptying
decrease appetite
```
SIDES: nausea, diarrhoea, vomiting, weight loss, immune reaction (antibody complex), pancreatitis, neoplasia (endocrine)
180
DPP-IV Inhibitor
Treatment of Type II Diabetes
Increase native GLP-1 levels
Increase insulin
Decrease glucagon
only as adjunct to diet and exercise!
SIDES: URTIs, headaches, hypersensitivity, pancreatitis, contraindicated w/ insulin -> hypoglycaemia
181
Phentermine (Duromine)
Used for Obesity
Amphetamine Derivative
Increases NA, DA, & 5HT (competes/blocks reuptake)
Suppresses appetite
Only useful in short term (tolerance & addiction)
SIDES: Increased BP, HR, insomnia, nervousness, headache, dry mouth
182
Topiramate (Topamax)
```
Used for Epilepsy / Migrane / Obesity
mechanism unknown (suppress appetite, increase energy expenditure)
```
SIDES: dizziness, taste alteration, teratogenic
183
5-flurocystosine
Prodrug activated by fungi and converted to 5-Flurouracil
5-FU also used in cancer treament
184
Drug classes used in bone disorders (antiresorptive vs anabolic)
ANTIRESORPITIVE
- Bisphosphonates
- SERMs
- RANKL inhibitors
BONE ANABOLIC AGENTS
- PTH
- Oral Calcium
- Oral Vitamin D analogues
- Calcitonin
185
Bisphosphonates (e.g. Alendronate)
Enzyme resistant analogue of pyrophosphate
Incorporated into bone matrix and ingested by osteoclasts during resorption
Inhibit recruitment of osteoclasts
Promote apoptosis of osteoclasts
= reduced fracture risk
Weekly administration. Poor Absorption. Risk for oesophagitis (due to reflux) and oesophageal cancer
186
Raloxifene
Selective oestrogen receptor modulator
Breast & endometrium - antagonist
Bone - agonist
Used in treatment of osteoporosis instead of HRT
Oestrogen decreases osteoclast proliferation, differentiation and activation, and promotes apoptosis
Increases lifespan of osteoblasts and osteocytes
Maintains bone mass and slows bone loss
Increased risk of CVD
187
Denosumab
RANKL inhibitor
Reduces osteoclastic activity
Treatment of osteoporosis
188
Rimonabant
CB1 antagonist
Anorectic
Withdrawn - suicidal thinking
189
Effect of Exercise on Exogenous Insulin
Plasma [insulin] increased
```
dependent on:
type, duration, intensity
muscle mass
level of fitness
carbohydrate supplementation
can cause hyperglycaemia or hypoglycaemia
```
190
Effect of Exercise on GTN (transdermal)
Plasma [GTN] increased
mechanisms:
increased skin blood flow = increased transdermal absorption
excess vasodilation may cause hypotension
191
Effect of Exercise on Salbutamol
Plasma [salbutamol] increased
mechanisms:
increased resp rate
increased pulmonary blood flow
increased epithelial permeability
192
Effect of Exercise on Oral Drugs (GI)
inhibition of gastric emptying (reduced drug delivery)
increased intestinal motility (less time for absorption)
decreased splanchnic blood flow
193
Effect of Exercise on Digoxin
Plasma [digoxin] lowered
Muscle [digoxin] increased
mechanism:
increased binding to skeletal muscles
therefore reduced ability to control heart rate
194
Effect of Exercise on Warfarin
Plasma [warfarin] decreased
```
mechanism:
increased sweating
lowered blood volume
increased binding to albumin
= decreased FREE warfarin
```
195
Effect of Exercise on β-blockers
```
Plasma [propanolol] increased
- reduced hepatic clearance)
Plasma [atenolol] increased
- reduced renal clearance
Plasma [carvedilol] same
```
196
Azithromycin
Treatment of Chlamydia (reticulate form) and Gonorrhoea
Attains high intracellular concentrations
Macrolide - Binds to the 50S subunit of the bacterial ribosome, and thus inhibits translation of mRNA
197
Acyclovir
Nucleoside analog without 3' -OH
used in treatment of herpes
herpesvirus thymidine kinase phosphorylates nucleoside to nucleotide
DNA polymerase adds nucleotide into viral DNA and ends transcription
valacyclovir similar but has Valine group which is removed by cellular enzymes (better bioavailability)
198
Ribavirin
```
Nucleoside analog with 2' -OH
works on DNA and RNA viruses
RSV
Influenza
Haemorrhagic fevers (ebola)
Hepatits C
```
199
HIV - Fusion/Entry Inhibitors
- bind CD4 and inhibit
- bind CCR5 (Maraviroc) or CXCR4 and inhibit
- bind gp41 trimer on HIV (Enfuviritde & T20 fusion inhibitor)
200
HIV - Reverse Transcriptase Inhibitors
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
- nucleoside analogues (phosphorylated by viral enzyme)
- reduce infection of new cells but can't eliminate virus
- Azidothymidine (thymidine analogue lacking 3' -OH )
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
- directly inhibit reverse transcriptase enzyme by other mechanisms
201
HIV - Integrase inhibitors
Inhibits integration of cDNA into cellular DNA
Raltegravir binds to active site of integrase enzyme
cDNA degrades or forms dead-end circle
202
HIV - Protease inhibitors
Saquinavir and Indinavir
bind to active site of protease enzyme
prevent cleavage of polyproteins into matrix, capsid, enzymes etc.
virus doesn't mature so particles are non-infectious
203
Emexestane
Aromatase inhibitor
(aromatase high in breast and adipose tissue)
- reduced synthesis of oestrogens
BENEFITS:
- reduced incidence of contralateral breast cancer
- reduced thromboembolic events
- reduced endometrial cancer incidence
RISKS:
- increased bone loss & fracture risk
- increased arthralgia
- poorer lipid profile, hepatic steatosis, metabolic syndrome
- menopausal signs
204
Finasteride
5a-reductase inhibitor
USES:
- benign prostatic hypertrophy
- hair loss
SIDES:
- impotence, decreased libido
- breast enlargement, tenderness, cancer
205
Cyproterone
steroidal androgen antagonist
deriverative of progesterone
antiandrogenic
USES:
- prostate cancer
- androgenisation in female
- oral contraceptive
- M2F
ADVERSE EFFECTS:
- higher risk of venous thromboembolic event
- cognitive changes, fatigue, odeema
- reduces spermatogenesis
206
Flutamide
non-steroidal androgen antagonist
USES:
- metastatic prostate cancer (+GnRH agonist)
ADVERSE EFFECTS:
- diarrhoea, anaemia
- oedema, dizziness, blurred vision
207
ethinyloestradiol
synthetic oestrogen used in oral contraceptives
208
norethisterone, levonorgestrel
Synthetic progesterones used in oral contraceptive pills
Slightly androgenic (acne, hirsutism)
Morning after pill is high dose (10x) of levonorgestrel
209
drospirenone
Synthetic progesterones used in oral contraceptive pills
Antiandrogenic
Mild diruetic (spironolactone derivative)
210
Codeine
```
Inactive
Demethylated in liver (to form morphine)
Morphine acts on u-opioid receptors
Greater bioavailability than morphine
Suppresses cough
Drowsiness/Sedation/Ventilatory depression
Decreases gut motility (causing constipation)
Can cause nausea/vomiting
```
combined with naloxone = Targin
211
Prialt
Analgesic (neuropathic pain)
Blocks subunit of pre-synaptic calcium channel
Given intrathecally (otherwise has effects on sympathetic nerves)
212
Lyrica, Neurotonin
Analgesic (neuropathic pain)
Reduces cell surface expression of pre-synaptic calcium channel
Effective for only 50% of patients
213
Oral Contraceptive Mechanism
- oestrogen
- progesterone
- adverse effects
- benefits
OESTROGENS
- negative feedback on anterior pituitary
- inhibit FSH therefore inhibit ovulation
PROGESTOGENS
- negative feedback on anterior pituitary and hypothalamus
- inhibit LH
- modifies cervical mucous (inhospitible for sperm)
- changes properties of endometrium (unfavourable for implantation)
- interfere with contractions of fallopian tubes
ADVERSE EFFECTS:
- hypertension
- venous thromboembolism (risk proportionate to dose)
- cancer (oestrogen only)
- nausea/vomiting
- flushing
- headache
- decreased libido
- depression/irritability/fatigue
BENEFITS:
- decreased cancer risk w/ progestogen (endometrial, ovarian, colorectal, breast)
- decreased risk of bone fracture
- protective for anaemia (reduction in oligomenorrhea)
214
Herceptin
binds HER2
Inhibits epidermal growth factor binding leading to cell death
Expensive
Used for breast cancer treatment
215
Oxytocin
- used in obstetric haemorrhage
- IV or IM administration
- stimulates smooth muscle contraction
SIDES: hypotension, tachycardia, water intoxication
216
Ergometrine
- used in obstetric haemorrhage (avoided with pre-eclampsia)
- IV or IM administration
- stimulates smooth muscle contraction (uterus and vascular smooth msucle)
SIDES: hypertension, nausea, vomiting
217
Labetalol
- alpha-antagonist (vasodilation)
- non selective beta-antagonist (prevent increased HR)
- used for pre-eclampsia
218
HIV treatments
- Miraviroc
- Enfuvirtide
- Zidovudine/AZT
- Nevirapine
- Raltegravir
- Saquinavir
Prevent binding to CCR5 (maraviroc)
Prevent hiv fusion to gp41 (enfuvirtide)
Nucleoside Reverse Transcriptase Inbitors (zidovudine/AZT)
Non-Nucleoside Reverse Transcriptase Inbitors (nevirapine)
Prevent Integrase (raltegravir)
Prevent viral polyprotein clevage and maturation (saquinavir)
Highly Active Anti-Retroviral Therapy = combination of above
- avoid resistance
- combination of partial antagonists
- inhibit cytochrome metabolism of active compounds
219
Targin
```
Combination analgesic
Oxycodone
- opioid analgesic
- u-receptor agonist
Naloxone
- used to treat opioid intoxication
- u-receptor antagonist
- primary action in GI tract
- prevent constipation of oxycodone
```
220
Transplant Immunosuppressive Drugs
Inhibit cytokines (prednisolone)
Cytotoxic (azathioprine)
Calcineurin inhibitors (cyclosporin)
Cytokine receptor antagonist (daclizumab anti-IL2)
T-lymphocyte depletion (anti-thymocyte globulin)
Inhibition of co-stimulation (abatacept anti-CTLA4)
221
Toxin types in Australian animal venoms
Neurotoxins
- ticks (ascending paralysis over days)
- snakes (neuromuscular block)
- death adder (no coagulopathy)
- redback (enhanced neurotransmitter release, sweating at bite site, painful)
- funnel web (fulminant, stimulate CNS, tachycardia, raised ICP, CNS depletion and hypotension)
Cytotoxins (necrosis)
- box jellyfish (cardiotoxicity)
Myotoxins
- brown snake (tiny fangs, may have no pain)
Anti/pro-coagulants
- butterfly/caterpillars/moth
- snakes (clotting & depletion of clotting factors = bruising and oozing at puncture site)
* venom allergy
- ants
- bees
222
Envenomation Investigations
Snake venom detection kit (bite site > urine > blood)
Check clotting & fibrinogen
d-dimer (fragmentation of clot)
Renal function (rhabdomyolysis - K+ & CK)
Haemolysis
223
Cephalosporins
MECHANISM:
Beta lactam - disrupt synthesis of peptidoglycan for cell wall
```
BACTERIA:
GPs (1st gen)
GPs & some GNs (2nd gen)
GNs & some GPs inc. gonorrhea and syphilis (3rd gen)
Pseudomonas (4th Gen)
MRSA (5th gen)
```
```
NAMES:
Cefazolin
Cefalexin
Cefotoxin
Cefixime
Cefotaxime
Ceftriaxone (STIs)
```
SIDES:
GI upset, nausea, diarrhea, allergy
224
Macrolides
MECHANISM:
Bind to 50s ribosome
BACTERIA:
Strep
Syphilis/Chlamydia
URTIs/LRTIs
NAMES:
Azithromycin
SIDES:
Nausea, Hearing Loss, Jaundice
225
Penicillins
MECHANISM:
Beta-lactam - disrupt synthesis of peptidoglycan cell wall
BACTERIA:
Strep
Syphilis
```
NAMES:
Amoxicillin
Ampicillin
Carbenicillin
Flucloxacillin
Methicillin
Penicillin G
Penicillin V
Piperacillin
Ticarcillin
```
SIDES:
GI upset, allergy
226
Quinolones
MECHANISM:
Inbibit DNA gyrase - thereby inhibiting DNA replication
BACTERIA:
UTIs
pneumonia
Gonorrhoea
NAMES:
Ciprofloxacin
227
Amantadine / Rimantadine
Antivirals for treatment of influenza
| Block M2 ion channel thereby inhibiting uncoating of virus/endosome
