DRUGS 🤯🤕 Flashcards
Oestrogen
Builds endometrium
- Produced by follicles
- Negative feedback on GnRH, LH & FSH secretion
- Tamoxifen competes w estrogen for its R
Allowing ER dimerisation but preventing co-activators from binding to the dimer on the ERE DNA element
Progestin
Stabilises endometrium
- Produced by follicles
- Helps implantation of fertilised ovum
- Negative feedback on GnRH & LH secretion (to prevent ovulation)
Side effects:
- irregular menstrual or vaginal bleeding
- inhibition of luteinising hormone secretion
- reduction in androgen-dependent acne
- prevention of sperm entry into uterus
Inhibin
Inhibits FSH secretion to prevent another follicle from forming
Released by corpus luteum (dead follicle that has released egg already)
FSH
Stimulates follicle maturation in ovaries
Produced in anterior pituitary
LH
Stimulates release of ovum
Produced in anterior pituitary
GnRH
Stimulates FSH & LH secretion by anterior pituitary
Produced in hypothalamus
Progestin only pill
- Creates a mucus plug in the cervix to prevent further sperm penetration
- Prevents LH surge → essentially prevents future ovulation but cannot stop already released egg from being fertilised
- Oestrogens should not be given without progestins to women with uterus
- Oestrogens cause hyperproliferation of endometrium = endometrial cancer
- Side effect of progestin only = irregular menstrual bleeding and high failure rate if improperly used
Combined pill
With estrogen:
Estrogen inhibits FSH
Preventing follicle maturation
Hormone replacement for menopause/emergency contraception
pretty much same action as two pills but since higher doses they can be used for hormone replacement therapy or for emergency contraceptive
Mifepristone
Pregnancy Termination (antiprogestin)
Levonorgestrel
‘Morning after’/emergency pill
Progestin competitive inhibitor)
High progestin dose
Prevents LH surge - prevents/delays ovulation
(Only work if taken 2 days before LH surge)
Doesn’t affect foetus
Ulipristal
Morning after’ pill
Progestin competitive inhibitor
High progestin dose
Inhibits progesterone binding to receptor (exact mechanism unknown)
Prevents/delays ovulation
Letrozole & Anastrozole
P450 Aromatase Inhibitors
Block androgen binding to aromatase active site (more specifically blocks conversion of testosterone to oestradiol and conversion of androstenedione to oestrone).
Reduces oestrogen synthesis
Tamoxifen
Oestrogen receptor inhibition
Tamoxifen is metabolised to 4-hydroxytamoxifen by liver (CYP2D6/CYP3A4), entering the cell.
Binds to oestrogen receptor allowing receptor dimerisation but preventing further binding of co-activators, preventing
gene transcription (more specifically oestrogen response elements) in cells
Lack of conformational change of oestrogen receptor results in no gene transcription
Alprostadil
(PGE pathway)
Increases PGE1
Injectable into the corpus cavernosa?
Painful (as PGE is an inflammatory molecule).
Papaverine
PDE pathway
Unknown - Proposed to inhibit phosphodiesterase 5
Causes vasodilation
Only used if alprostadil is contraindicated
No localised pain
Phentolamine
Adrenergic nerve inhibitor
Competitive antagonism of alpha-1 adrenoreceptors
Causes vasodilation
Inhibits the action of adrenergic nerve stimulation which is smooth muscle contraction (think SNS → fight or flight so vasoconstriction in non-essential organs)
By inhibiting this vasoconstriction it promotes vasodilation
Levitra - Vardenafil
Viagra - Sildenafil
Cialis Tadalafil
=Lower dose & longer duration of action
Think ‘fils’ fill the corpus cavernosum with blood through vasodilation
PDE5 inhibitors
Take pill 1-2h before intercourse
Still needs stimulation from NANC nerves
prevents degradation of cGMP to 5’-GMP to allow endogenous NO to be more effective
Metabolised/inactivated by P450 3A4
QUICK NOTE HOW SMOKING DISRUPTS DRUG FUNCTION:
Damages Endothelial cell resulting in release of vasoconstrictors, harden blood vessels, decreasing penile blood flow,
Increases RADICALS (superoxide & peroxy nitrite) that decrease NOS activity
Increased SNS (sympathetic nervous system) tone
Finasteride
Dutasteride
- Better and more consistent therapy than finasteride
Ideally drug of choice
Inhibits 5AR (5-alpha-reductase) and decreases DHT (5-alpha-dihydrotestosterone
Reduces prostate size and reduces pressure of bladder and urethra
Used for benign prostatic hyperplasia (enlarged prostate)
Finasteride can also be used for androgenic alopecia (male pattern balding).
Alfuzosin & Tamsulosin
Alpha-1A selective (specific for prostate gland and bladder neck)
Less cardiac side effects
Less effective against benign prostatic hyperplasia but also less hypotension
Reduces degree of smooth muscle contraction in prostate to reduce pressure on urethra and increase urinary flow.
Specific for alpha-1 and won’t induce tachycardia via alpha-2 receptors
Prazosin & Terazosin
Less receptor selectivity
More effective in BPH treatment but dose titration is needed to minimise hypotensive effects
Reduces degree of smooth muscle contraction in prostate to reduce pressure on urethra and increase urinary flow.
Specific for alpha-1 and won’t induce tachycardia via alpha-2 receptors
Thalidomide
R enantiomer: sedative
S enantiomer: teratogenic
Used for morning sickness due to sedative effects of R enantiomer, but S enantiomer caused birth defects
Pilocarpine
Muscarinic ACH agonist
SLUDGE BBB
Carbachol
Muscarinic ACH agonist
SLUDGE BBB
Atropine
Anticholinergic/competitive reversible muscarinic antagonist
Anti-sludge BBB
Muscarine
Agonist of muscarinic acetylcholine R
SLUDGE BBB
Scopolamine
Anticholinergics or Competitive reversible muscarinic antagonist
Anti-sludge BBB
Acetylcholine
Agonist of nicotinic and muscarinic acetylcholine receptor.
SLUDGE BBB
Adrenaline
Physiological antagonist of acetylcholine - binds to adrenergic receptors, causing opposite effects.
Pyridostigmine
Acetylcholinesterase inhibitor ‘stigmines’ - increases acetylcholine concentrations.
SLUDGE-BBB
Class I: Antidysrhythmics
Sodium Channel Block (e.g. lignocaine)
Block voltage gated sodium channels by preferentially binding to inactivated state, reducing sodium influx and membrane depolarisation.
Class II
Beta adrenoceptor antagonism (Beta blockers)
Blocks beta 1 and beta 2 receptors
Block sympathetic activity, decreasing cAMP
Class III:
Potassium channel block
Prolong cardiac action potential, increasing refractory period of sodium channels, preventing reentrant tachycardia and suppressing ectopic activity.
Prolonged plateau phase
Class IV:
Calcium channel block (e.g. verapamil and diltiazem)
Calcium channel antagonists
Slow conduction in the SA and AV nodes, reduced calcium entry, also reduces the after-depolarisation. Calcium antagonists will also reduce contractile force
Shortened plateau phase
Adenosine
Acts on adenosine receptors
Makes pacemakers less excitable
Opening of K+ channels and hyperpolarization
Used for tachycardia
Atropine
Competitive antagonist of muscarinic receptors. Removes the parasympathetic brake on the heart rate
Used for sinus bradycardia
Isoprenaline
Beta agonist sympathomimetic
produces a positive inotropic and chronotropic effect
Treatment of heart block or bradycardia with haemodynamic compromise
Adrenaline
Non-specific agonist for adrenergic receptors.
Produces a positive ionotropic and chronotropic effect.
Used for cardiac arrest
Ivabradine
New drug:
Coronary heart disease
Chronic heart failure
Benzodiazepines(BNZ)
Antiepileptic drugs
Binds to alpha 1 (VTA) → reduction of GABA release → Increase GABA release
Barbiturates
Similar to BNZ + inducer of P450s
Valproate
Is a T-type calcium channel blocker (which is why it is helpful to treat absences, since they are caused by abnormalities in these channels.
Calcium channel blockers (e.g. valproate and ethosuximide)
Block T-type channels contributing to rhythmic discharges in thalamus involved in absence seizures.
Morphine
Opioid:
Full agonist of opioid receptor
Via µ opioid receptors (which work as G protein-coupled receptors which inhibit adenylate cyclase activity, open K+ channels and inhibit the opening of Ca2+ channels in nerve endings), opioids inhibit the release of neurotransmitters like substance P from nerve terminals, leading to suppression of asc/desc pain pathway signalling.
Kappa receptors can exert additional effect on spinal cord.
