Pharmacology of drugs

β-adrenoceptor agonists

• Isoprenaline is a full agonist that binds to β1 and β2 receptors, causing increased heart rate and contraction.
• Salbutamol, Terbutaline, Salmetarol, and Formoterol are partial agonists that primarily target β2 receptors.
• Salbutamol and Terbutaline are short-acting β-adrenoceptor agonists (SABAs) used for acute asthma treatment.
• Salmetarol and Formoterol are long-acting β-adrenoceptor agonists (LABAs) used for asthma prevention.
• LABAs must be combined with inhaled corticosteroids.

Tyramine

• Tyramine is structurally similar to norepinephrine (NA).
• Tyramine is transported by the norepinephrine transporter (NET) into nerve terminals, limiting neuronal reuptake of NA.
• Tyramine displaces NA from vesicles and increases NA in the junction, leading to activation of post-junctional adrenoceptors.
• Tyramine can be metabolized by monoamine oxidase (MAO).

Biguanides

• Metformin is a biguanide used for type II diabetes.
• Metformin increases insulin-mediated glucose uptake.
• Metformin reduces hepatic glucose production by activating AMP-activated protein kinase in the liver.
• Metformin decreases carbohydrate absorption.
• Metformin reduces LDL cholesterol and triglyceride levels.

Sulfonylureas

• Sulfonylureas mimic the rapid peak in insulin that's absent in type II diabetes.
• Sulfonylureas act on β cells to stimulate insulin secretion.
• Sulfonylureas bind to K+ ATP channels, reducing K+ permeability and preventing K+ efflux.
• This causes membrane depolarization, triggering the opening of Ca2+ channels for Ca2+ entry and insulin release.

Na+ - glucose cotransporter 2 (SGLT-2) inhibitors

• SGLT-2 inhibitors increase the excretion of glucose.
• They work by inhibiting the SGLT2 transporter, which decreases the resorption of blood glucose from the proximal convoluted tubule (PCT).
• This leads to increased glucose excretion.

α-glucosidase inhibitors

• α-glucosidase inhibitors inhibit intestinal α-glucosidase, which digests carbohydrates.
• This delays carbohydrate absorption, allowing undigested carbs to reach the distal bowel for longer.
• α-glucosidase inhibitors decrease the post-prandial rise in glucose.

Exogenous insulin

• Exogenous insulin increases insulin to physiological levels.
• It can interact with various drugs, including beta-blockers, corticosteroids, diuretics, and alcohol.

Dopamine reuptake inhibitors

• Methylphenidate (Ritalin) and Atomoxetine (Strattera) are dopamine reuptake inhibitors used for ADHD.
• They increase synaptic concentrations of dopamine by blocking reuptake.

Selective NA reuptake inhibitors

• Reboxetine is a selective NA reuptake inhibitor used for depression.

Modafinil

• Modafinil (Provigil) is a wakefulness-promoting agent used for learning and narcolepsy.
• Its exact mechanism of action is unclear.

Glyceryl Trinitrate (GTN)

• GTN is a prodrug that's converted to nitric oxide (NO).
• NO stimulates guanylate cyclase in vascular smooth muscle, increasing cGMP.
• This leads to vasodilation of collateral vessels, increasing oxygen supply and decreasing oxygen demand.

Glucagon-like peptide (GLP) 1 agonists

• Liraglutide is a GLP-1 agonist used for obesity.
• GLP-1 agonists mimic the effects of endogenous GLP-1, binding to GLP-1 receptors on the vagus nerve.

H2 receptor antagonist

• Cimetidine and Famotidine are H2 receptor antagonists that competitively bind to the H2 receptor, blocking the binding of histamine on gastric parietal cells.
• This reduces acid secretion.

Proton pump inhibitors

• Omeprazole is a proton pump inhibitor that requires an acidic environment to activate.
• It inhibits the proton pump, further reducing acid secretion.

Dopamine Agonist

• Bromocriptine and Cabergoline are dopamine agonists
• Both can be used as a monotherapy for Parkinson’s Disease
• They act by stimulating the release of dopamine
• Bromocriptine is not as targeted as Cabergoline which binds to all dopamine receptors
• Bromocriptine is not as safe as Cabergoline as the latter is safe for asthmatics
• Bromocriptine can cause hallucinations
• Cabergoline improves bradykinesia and rigidity

L-DOPA

• L-DOPA is an effective treatment for Parkinson’s Disease
• L-DOPA is a precursor to dopamine
• The conversion of L-DOPA to dopamine is stimulated by the dopamine decarboxylase enzyme
• Both Bromocriptine and Cabergoline can be used as a monotherapy for Parkinson’s Disease
• L-DOPA can make Parkinson’s symptoms worse overtime due to the degeneration of dopaminergic neurons
• L-DOPA can cause dysrhythmias, orthostatic hypotension, pupil dilation, visual and auditory hallucinations, abnormal motor movement, mood changes, depression and anxiety

Ca+ Channel Antagonists

• Dihydropyridines, Benzothiazepines and Phenylalkylamines are all Ca+ channel antagonists
• All three act by preventing channels opening, thereby decreasing intracellular Ca2+ levels
• They all decrease vascular contractile tone and BP
• They may cause initial reflex tachycardia
• Dihydropyridines are often used to treat angina pectoris
• Benzothiazepines are often used to treat hypertension
• Phenylalkylamines are often used to treat supraventricular tachycardias

Glyceryl Trinitrate

• Glyceryl Trinitrate (GTN) is a prodrug that’s converted to NO
• It stimulates guanylate cyclase in vascular smooth muscle
• It increases cGMP which increases vasodilation of collateral vessels
• It is typically administered sublingually to avoid first pass metabolism by the liver
• It may cause reflex tachycardia and increased vascular tone
• It may cause venous pooling and postural hypotension

Glucagon-like Peptide (GLP) 1 Agonist

• Liraglutide is a GLP1 agonist
• It’s used for obesity and type 2 diabetes
• GLP1 is released naturally from the L cells in response to carbs, fats and proteins
• GLP1 agonists mimic the effects of the endogenous GLP1 released by L cells
• It binds to the GLP1 receptors on the vagus nerve
• It can cause nausea, vomiting, diarrhoea and injection site reactions
• It can cause pancreatitis although this is rare

H2 Receptor Antagonist

• Cimetidine is an H2 receptor antagonist
• It competitively binds to the H2 receptor which blocks the histamine binding to the parietal cells
• It reduces gastric acid secretion
• It’s used for peptic ulcer disease, GORD and dyspepsia.
• It is a non-selective inhibitor of CYP450
• It can interact with CYP450 enzymes and increase levels of other drugs

Proton Pump Inhibitors

• Omeprazole is a proton pump inhibitor
• It is a prodrug
• It requires an acidic environment for activation
• It’s used in combination with other drugs such as Acyclovir
• It can cause constipation

Anti-HIV Drugs

• NRTIs and NNRTIs are anti-HIV drugs
• They are highly selective for HIV reverse transcriptase
• Protease inhibitors also inhibit HIV replication
• These drugs inhibit the reverse transcriptase enzyme to produce a double DNA strand

COVID-19 Drugs

• Sotrovimab, Remdesivir and Molnupiravir are all used for COVID-19
• Sotrovimab binds to spike proteins to prevent infection
• Remdesivir is a viral polymerase inhibitor
• Molnupiravir is also a viral polymerase inhibitor which implants mutations to inhibit viral growth

Cytotoxic Agents

• Cisplatin and Methotrexate are cytotoxic agents
• These are used for chemotherapy
• Cisplatin binds covalently to cell components
• It can cause severe nausea and vomiting, nephrotoxicity and neurotoxicity
• Methotrexate inhibits folate synthesis by inhibiting DHFR
• It's an immunosuppressant drug