Unit 12 Drugs Flashcards
Spironolactone
CLASS:
K⁺-sparing diuretic
PHARMACOLOGY
Target: Mineralocorticoid Receptor
Activity: competitive antagonist
PHYSIOLOGY
Antagonises action of aldosterone in late DCT/CD
↓ expression of ENaCs and Na⁺/K⁺-ATPase
Weak diuretic effect (most Na⁺ already reabsorbed)
K⁺ retention → hyperkalaemia
CLINICAL
Often used with thiazide/loop to offset K⁺ loss
Hypertension; oedema; heart failure
Amiloride
CLASS:
K⁺-sparing diuretic
PHARMACOLOGY
Target: Epithelial Na channel (ENaCs)
Activity: channel blocker
PHYSIOLOGY
↓ Na⁺ entry from lumen of DCT into cell
Rate-limiting step of Na⁺ reabsorption
Weak diuretic effect (most Na⁺ already reabsorbed)
K⁺ retention → hyperkalaemia
CLINICAL
Used with thiazide/loop to offset K⁺ loss
Hypertension; oedema; heart failure – notoften used in CHF
What drugs inhibit Na+/K+ ATPase pumps?
Cardiac glycosides e.g., digoxin
List some antihypertensive drugs
- Diuretics (thiazides, loops, K sparing)
- Renin inhibitor
- ACE inhibitos (-pril)
- Angiotensin recptor blocker (-sartan)
- B blockers (-lol)
- Calcium channel blockers (-dipine)
- Centrally acting a2 agonists e.g., clonidine
- Vasodilators
Aliskiren
CLASS:
renin inhibitor
PHARMACOLOGY:
Target: renin
Activity: competitive inhibitor
PHYSIOLOGY
: ↓production of AT-I → ↓RAAS activation
CLINICAL
: Essential Hypertension
Enalapril
CLASS: ACE inhibitor (ACEI)
Pro-drug: converted to active metabolite → enalaprilat
PHARMACOLOGY:
Target: ACE
Activity: competitive inhibitor
PHYSIOLOGY:
↓production of AT-II
↓breakdown of bradykinin (vasodilator)
CLINICAL:
Essential hypertension
Heart failure
Valsartan
CLASS: angiotensin receptor blocker (ARB)
PHARMACOLOGY:
Target: AT₁ (receptor)
Activity: competitive antagonist
PHYSIOLOGY:
↓ effects of AT-II
No effect on bradykinin → no cough
CLINICAL:
Essential hypertension
Heart failure
Atenolol
CLASS: Selective β₁ blocker
PHARMACOLOGY:
Target: β₁ receptor
Activity: competitive antagonist
PHYSIOLOGY: (is not understood)
↓cardiac output
Alter baroreceptor reflexes
↓renin secretion
↓sympathetic outflow (central)
CLINICAL:
Essential hypertension
Angina
Arrhythmias
Amlodipine
CLASS: Calcium channel blocker
PHARMACOLOGY:
Target: L-typevoltage-gated calcium channels
Activity: gating inhibitor
PHYSIOLOGY:
smooth muscle > cardiac muscle
↓Ca²⁺ mobilisation in sm. muscle
→vasodilation
CLINICAL:
Essential hypertension
Angina
Phentolamine
1* target= A1 receptor (GPCR)
Activity= antagonist (partial)
2* target= B1 receptor (GPCR)
Activity= Antagonist
smooth muscle relaxation— vasodilation.
partial blockage of alpha 1 receptors increases cardiac output through positive inotropic effects
Rivaroxiban
CLASS: NOAC = novel oral anticoagulant
Direct Factor Xa inhibitor
PHARMACOLOGY:
Target: FXa (prothrombinase complex)
Activity: competitive inhibitor
PHYSIOLOGY:
Anticoagulant
↓thrombin generation
CLINICAL:
Treatment/prophylaxis DVT & PE
Alteplase
CLASS: Fibrinolytic
PHARMACOLOGY:
Target: Plasminogen
Activity: activator
PHYSIOLOGY:
Promotes endogenous fibrinolytic system
Thrombus dissolution
CLINICAL:
Acute myocardial infarction
Pulmonary embolism
Ischaemic stroke
Dabigatran
CLASS: NOAC = novel oral anticoagulant
Direct thrombin inhibitor
Prodrug, non-peptide
PHARMACOLOGY:
Target: thrombin FIIa (enzyme)
Activity: competitive, reversible inhibitor
PHYSIOLOGY:
Anticoagulant; ↓fibrin formation
↓thrombin-induced platelet aggregation
CLINICAL:
Treatment/prophylaxis DVT & PE
Furosemide
CLASS:
Loop diuretic
PHARMACOLOGY
Target: Na⁺-K⁺-Cl⁻ symporter
Activity: Inhibitor
PHYSIOLOGY
↓Na⁺ reabsorption in thick ascending Loop of Henle → ↑urine flow
Potent diuretic action
↑↑ K⁺ loss → hypokalaemia (& metabolic alkalosis)
Secreted by OATs (organic anion transporters) in PCT → ↑↑ concentration in tubules
↓uric acid secretion (competes for OATs) → uricaemia → ↑risk of gout
CLINICAL
Hypertension; oedema; heart failure
Hydrochlorothiazide
CLASS:
Thiazide diuretic
PHARMACOLOGY
Target: Na⁺-Cl⁻ symporter
Activity: Inhibitor
PHYSIOLOGY
↓Na⁺ reabsorption in DCT → ↑urine flow
Mild diuretic action
Some loss of HCO₃⁻ → metabolic alkalosis
↑K⁺ loss → hypokalaemia
Secreted by OATs (organic anion transporters) into PCT → ↑concentration in tubule lumen
↓uric acid secretion (competes for OATs) → uricaemia → ↑risk of gout
CLINICAL
Hypertension; oedema
Acetazolamide
CLASS:
Carbonic Anhydrase Inhibitor
PHARMACOLOGY
Target: carbonic anhydrases
Activity: Competitive inhibitor
PHYSIOLOGY
↓Na⁺ reabsorption in PCT → ↑urine flow
~⅓ PCT Na⁺ reabsorption is through Na⁺/H⁺ antiporter
Diuretic effect is mild and self-limiting
→ ↓ preload → ↓ venous congestion → symptomatic relief
Heavy loss of HCO₃⁻ → alkaline urine/metabolic acidosis → ↓diuresis
↑Na⁺ at DCT → ↑K⁺ loss → hypokalaemia
CLINICAL
Diuretic
Still in use for glaucoma
Mannitol
CLASS:
Osmotic diuretic
PHARMACOLOGY
Target: NONE !!!!!!!
Activity: NONE !!!!!!!
PHYSIOLOGY
Does not cross membranes
Raises osmotic pressure → draws fluid to itself
Response proportional to concentration
Very potent diuretic
Substantial K⁺ loss
CLINICAL
IV injection
Used ACUTELY → rapid loss of fluid, e.g., cerebral oedema
NOT used in chronic hypertension; congestive heart failure
Dapaglifozin
CLASS:
SGLT2 inhibitor
PHARMACOLOGY
Target: SGLT2 Sodium/glucose co-transporter 2 (expressed in early PCT, have low affinity & high capacity, 1 Na+:1 glucose)
Activity: Competitive inhibitor
PHYSIOLOGY
↓ glucose reabsorption in PCT → glycosuria → osmotic diuresis
↓ Na⁺ reabsorption in PCT → natriuresis
↓ blood glucose
CLINICAL
Diabetes mellitus (mostly Type II)
Congestive heart failure
Sacubitril
CLASS:
Neprilysin inhibitor (-tril)
Prodrug: active metabolite
PHARMACOLOGY
Target: Neprilysin (enzyme)
Activity: Competitive inhibitor
PHYSIOLOGY
Neprilysin cleaves/degrades ANP & BNP
Hence, sacubitril ↑ ANP/BNP levels
CLINICAL
Congestive heart failure
ANP & BNP
CLASS:
Natriuretic peptides
PHARMACOLOGY
Target: Natriuretic Peptide Receptor 1 = NPR1 (also NPR2 & NPR3)
Activity: agonist
PHYSIOLOGY
NPR1 widely expressed, including kidney
Guanylyl cyclase converts GTP → cGMP → ↑PKG activity
→ inhibition of ENaC and Na⁺/K⁺-ATPase in collecting duct
→ ↑ GFR ↓ renin release → ↓ ECF
Oppose action of AT-II and aldosterone
CLINICAL
Sacubitril effectively ↑ activity of ANP/BNP
Digoxin
CLASS:
Cardiac glycoside
PHARMACOLOGY
Target: Na⁺/K⁺-ATPase (sodium pump)
Activity: Competitive inhibitor (K⁺ binding site)
PHYSIOLOGY
Na⁺/Ca²⁺(3Na+ in : 1 Ca2+ out) exchanger (NCX) removes Ca²⁺ from cytoplasm during diastole
↑ [Na⁺]ᵢ → ↓ driving force for Ca²⁺ extrusion →
↑ [Ca²⁺]ᵢ → ↑ force of contraction +ve inotropic effect)
↓ oedema (dropsy)
TOXIC – low therapeutic index (interaction with diuretics)
CLINICAL
Atrial fibrillation: ↓AV node conduction
Congestive heart failure
Ivabradine
PHARMACOLOGY
Target: HCN channels (‘funny’ current) (HCN = Hyperpolarisation and Cyclic Nucleotide-gated)
Activity: Antagonist
PHYSIOLOGY
Inhibiting If current (The pacemaker current (or If, or IKf, also referred to as the funny current) is an electric currentin the heart that flows through the HCN channel or pacemaker channel) →↓ heart rate →↓ cardiac work
CLINICAL
Angina
Congestive heart failure
Hydralazine
CLASS:
Vasodilator
PHARMACOLOGY
Target: unknown !!
Activity: unknown?
PHYSIOLOGY
Vasodilator
May block IP₃-dependent Ca²⁺ release from SR
CLINICAL
Anti-hypertensive
Congestive heart failure (used with nitrates)
Salbutamol
CLASS: Short-Acting B2 agonist (SABA)
CHEMSITRY: small molecule, analogue of adrenaline
PHARMACOLOGY: 1* target- B2 adrenoceptor (GPCR)
Activity- partial agonist
Selectivity- B2>B1 not massively tho. targets lungs → into blood→ heart has B1 receptors → increased HR
PHYSIOLOGY: B2 receptors present on smooth muscle cells (and mast cells)
GS –> ↑adenylyl cyclase –> cAMP –> ↑cAMP –> ↑PKA and decreased Ca2+ in cells –>deactivate MLC kinase and activate MLC phosphatase–> s.m. relaxation
Bronchodilation, tocolytic (stops labor) and casuses vasodilation in cap beds
Increased cAMP caused decreased degranulation of mast cells
CLINICAL: obstructive airway disease, premature labor, performance enhancement
Budesonide
CLASS: inhaled corticosteroid (ICS)
CHEMISTRY: synthetic glucocorticoid
PHARMACOLOGY: 1* target: glucocorticoid receptor (nuclear hormone receptor)
Activity: agonist
PHYSIOLOGY: transrepression: decreases pro-inflammatory mediators
transactivation: increases anti-inflammatory mediators
CLINICAL: Anti-inflammatory
Immunosuppressive
Montelukast
CLASS: LeukoTriene Receptor Antagonist (LTRA)
CHEMISTRY: synthetic analogue of leukotriene
PHARMACOLOGY: 1* target: CysLT1 (GPCR)
Activity: Competitive antagonist
PHYSIOLOGY: LT’s are inflammatory mediators derived from arachidonic acid. They result in smooth muscle contraction, vascular permeability and leukocyte activation
CLINICAL: prophylaxis of asthma
Omalizumab
CHEMISYRY: humanised monoclonal igG1
PHARMACOLOGY: target: unbound IgE heavy chain constant
Activity: neutralising/ blocking
PHYSIOLOGY:
Decreases binding of IgE to FCσR1 receptor on mast cells/ basophils therefore decreased allergen inducing mediator release
CLINICAL: prophylaxis for severe allergic asthma
Mepolizumab and reslizumab
CHEMISTRY: Humanised monoclonal IgG
PHARMACOLOGY: target: Il-5
Activity: neutralise/ block
PHYSIOLOGY: Il-5 is important in growth, differentiation, recruitment, activation and survival of eosinophils.
CLINICAL: severe eosinophilic asthma
Benralizumab
CHEMSITRY: humanised monoclonal IgG
PHYSIOLOGY: Target: Il-5 receptor on eosino/basophils
Action: Fc region also binds to immune cells- tagrteing the eosino/basophil for destruction
CLINICAL: severe eosoinophilic asthma
tiotropium
CLASS: long acting muscarinic antagonist (LAMA)
CHEMISTRY: synthetic nalgoue of atropine
PHARMACOLOGY: 1* target: m3 receptor Activity: non selective competitive antagonist
PHYSIOLOGY: Ach→M3→Gaq… increase in cytosolic Ca2+→ contraction and mucous secretion
antagonism causes bronchodilation and decreased secretion
Target symmpathetic action of sm.muscle
